Researh & development

Cell Differentiation and Pathology Lab


Our laboratory works to understand the molecular mechanisms that regulate the formation of skeletal muscle and how these are affected in musculoskeletal dystrophies. We have conducted extensive studies to understand the role of the extracellular matrix (ECM) in the formation and regeneration of skeletal muscle and understand the fibrotic phenomena associated with skeletal muscle dystrophies.

We are interested in understanding the mechanisms involved in fibrosis associated with musculoskeletal diseases. Muscle fibrosis corresponds to an increase in ECM components, which occurs in skeletal muscle. This occurs, for example, in muscular dystrophies, such as Duchenne muscular dystrophy (DMD), muscle denervation due to loss of motor activity (ALS), or in sarcopenia associated with aging. We studied the role of pro-fibrotic factors (TGF-beta, CTGF/CCN2), different components of the renin-angiotensin system (RAS), and lysophosphatidic acid LPA in the genesis of skeletal muscle fibrosis. Furthermore, we are interested in understanding the cell type(s) responsible for the fibrotic response in different muscle models. Thus we have found several inhibitors of pro-fibrotic factors that are effective in improving muscle pathophysiology and correspond to essential proofs of concept in Translational Medicine. Some of these inhibitors have been used in human patients (Phases 2 and 3 in clinical trials).


Ph.D. students.

  • María José Acuña, Ph.D. Curr. Pos. Assistant Professor, Universidad Bernardo O’Higgins, Santiago, Chile
  • Claudio Cabello-Verrugio, Ph.D. Curr. Pos. Full Professor, Universidad Andrés Bello, Santiago, Chile
  • Daniel Cabrera, Ph.D. Curr. Pos. Research Associate, P. Universidad Católica de Chile, Santiago, Chile
  • Juan Carlos Casar, MD/Ph.D. Curr. Pos. Assistant Professor, P. Universidad Católica de Chile, Santiago, Chile
  • Rebeca Droguett, Ph.D. Curr. Pos. Teacher in Science, Santiago, College, Santiago, Chile
  • Jaime Gutierrez, Ph.D. Curr. Pos. Associate Professor, Universidad San Sebastián, Santiago, Chile
  • Juan Pablo Henríquez, Ph.D. Curr. Pos. Full Professor, Universidad de Concepción, Concepción, Chile
  • Claudia Hurtado, Ph.D. Curr. Pos. Research Associate. Clínica Las Condes, Santiago, Chile
  • Juan Larraín, Ph.D. Curr. Pos. Full Professor, P. Universidad Católica de Chile, Santiago, Chile
  • Valeria Mezzano, M.D./Ph.D. Curr. Pos. Assistant Professor, NYU Langone Medical Center, USA
  • María Gabriela Morales, Ph.D. Curr. Pos. Research Associate, University of Texas Southwestern M.C. USA
  • Hugo Olguín, Ph.D.  Curr. Pos. Associate Professor, P. Universidad Católica de Chile, Santiago, Chile
  • Nelson Osses, Ph.D. Curr. Pos. Full Professor, Universidad Católica de Valparaiso, Valparaíso, Chile
  • Cecilia Riquelme, Ph.D. Curr. Pos. Associate Professor, P. Universidad Católica de Chile, Santiago, Chile
  • Cecilia Vial, Ph.D. Curr. Pos. Associate Professor, Universidad del Desarrollo, Santiago, Chile.
  • Gonzalo Cordova, Ph.D. Curr. Pos. Scientific Editor Springer Nature B.V. Rotterdam, The Netherlands
  • Andrés Ramirez, Ph.D. Curr. Pos. Regional Specialist. United Arab Emirates
  • David Gonzalez, Curr. Pos. Postdoctoral Fellow. Institut des Neurosciences de Montpellier, France
  • Osvaldo Contreras, Ph.D. Victor Chang Cardiac Research Institute, Darlinghurst,  Australia
  • Roger Valle-Tenney, Ph.D. Université Catholique de Louvain, Belgium

Postdoctoral Fellows

  • Claudio Cabello-Verrugio, Ph.D. Curr. Pos. Full Professor, Universidad Andrés Bello, Santiago, Chile
  • Daniel Cabrera, Ph.D. Curr. Pos. Research Associate, P. Universidad Católica de Chile, Santiago, Chile
  • Cristián Droppelmann, Ph.D. Curr. Pos. Reasearch Associate, The University of Western Ontario, Canada
  • Verónica Eisner, Ph.D. Curr. Pos. Assistant Professor, P. Universidad Católica de Chile, Santiago, Chile
  • Jaime Gutiérrez, Ph.D. Curr. Pos. Associate Professor, Universidad San Sebastián, Santiago, Chile
  • Daniela Rebolledo, Ph.D. Independent Researcher, CEBIMA, Punta Arenas, Chile.
  • Cecilia Riquelme, Ph.D. Curr. Pos. Associate Professor, P. Universidad Católica de Chile, Santiago, Chile
  • Cecilia Vial, Ph.D. Curr. Pos. Associate Professor, Universidad del Desarrollo, Santiago, Chile.
  • Joan Villena, Ph.D. Curr. Pos. Assistant Professor, Universidad de Valparaíso, Valparaíso, Chile
  • Gonzalo Ugarte, Ph.D. Curr. Pos. Associate Professor, Universidad de Santiago, Santiago, Chile
  • Alexia Bock, Graduate Student, Biozentrum, University of Basel, Switzerland.
  • Adriana Córdova, Post Doctoral Fellow, University of Cambridge, UK.

National Collaborations

  • Dra. María José Acuña (Universidad Bernardo O´Higgins)
  • Dr. Claudio Cabello (Universidad Andrés Bello)
  • Dra. Verónica Eisner (P. Universidad Católica de Chile)

International Collaborations

  • Dr. Roel Goldschmeding (Utrecht University, The Netherlands)
  • Dr. Fabio Rossi (University of British Columbia, Canada)
  • Dra. Pura Muñoz-Canoves, (Pompeu Fagra University, Spain)
  • Dr. Jerold Chun (Sanford Burnham Prebys, USA)


Rojas, M., Brandan, E., and Zambrano, F. (1980) Salt loading effect on renal kallikrein activity in rat. Proc. Soc. Exp. Biol. Med. 171: 151 154.

Brandan, E., and Fleischer, B. (1982) Orientation and role of nucleoside diphosphatase and 5 nucleotidase in Golgi vesicles from rat liver. Biochemistry 21: 4640 4645.

Brandan, E., Rojas, M., Loyarte, N., and Zambrano, F. (1982) Golgi complex function in the excretion of renal kallikrein. Proc. Soc. Exp. Biol. Med. 171: 221 231.

Leighton, F., Brandan, E., Lazo, O., and Bronfman, M. (1982) Subcellular fractionations on the organization of the fatty acid oxidations by liver peroxisomes. Ann. N.Y. Acad. Sci. 386: 62 80.

Simion, T., Winek, D., Brandan, E., Fleischer, S., and Fleischer, B. (1983) Isolation and characterization of coated vesicles from rat liver. Methods in Enzymology 98: Part L, 326 330.

Brandan, E., and Inestrosa, N.C. (1984) Binding of the synaptic form of acetylcholinesterase to heparin. Biochem. J. 221: 415 422.

Brandan, E., Maldonado, E., Garrido, J., and Inestrosa, N.C. (1985) The anchorage of collagen tailed acetylcholinesterase to the extracellular matrix is mediated by heparan sulfate pro-teoglycans. J. Cell Biol. 101: 985 992.

Brandan, E., Llona, I., and Inestrosa, N.C. (1986) Heparin acetylcholinesterase interaction: Specific detachment of class I A forms, and binding of class I and II A forms to heparin agarose. Neurochem. Int. 9: 75 84.

Brandan, E., and Inestrosa, N.C. (1986) The synaptic form of acetylcholinesterase binds to cell surface heparan sulfate proteoglycans. J. Neurosci. Res. 15: 185 196.

Brandan, E., and Inestrosa, N.C. (1987)Isolation of the heparan sulfate proteoglycans from the extracellular matrix of rat skeletal muscle. J. Neurobiol. 18: 271 282.

Inestrosa, N.C., Nader, H.B., Garrido, J., Sampaio, L.O., Brandan, E., and Dietrich, C.P. (1987). Glycosaminoglycan Composition of Electric Organ Basement Membranes. J. Neurosci. Res. 17: 256 264.

Brandan, E., and Inestrosa, N.C. (1987) Co solubilization of asymmetric acetylcholinesterase and dermatan sulfate proteoglycan from the extracellular matrix of rat skeletal muscles. FEBS Lett. 213: 159 163.

Inestrosa, N.C., González, R., González, M.A, Perelman, A., Sánchez, J.P., Koenig, C., y Brandan, E. (1988)Investigación Biotecnológica en larvas de loco Concholepas concholepas. (Bru-giere, 1789) (Gastropoda, Muricidae) Biol. Pesq. 17: 73 94.

Brandan, E., and Hirschberg, C.B. (1988). Purification of rat liver N heparan sulfate sulfotransferase. J. Biol. Chem. 263: 2417 2422.

Brandan, E., and Hirschberg, C.B. (1989) Differential association of rat liver heparan sulfate proteoglycans between membranes of Golgi apparatus and the plasma membrane. J. Biol. Chem. 264: 10520 10526.

Perelman, A., and Brandan, E. (1989) Different membrane bound forms of acetylcholinesterase are present at the cell surface of hepatocytes. Eur. J. Biochem. 182: 203 207.

Inestrosa, N.C., Labarca, R., Perelman, A., Campos, E.O., Araneda, R., González, M., Brandan, E., Sánchez, J.P., y González Plaza, R. (1990) Aspectos biotecnológicos en larvas de loco. Arch. Biol. Med. Exp. 23: 179 186.

Fadic, R., Brandan, E., and Inestrosa, N.C. (1990) Motor nerve regulates muscle extracellular matrix proteoglycan expression. J. Neurosci. 10: 3516 3523.

Brandan, E., González, M., González Plaza, R., and Inestrosa, N.C. (1990) Increase of macromolecules synthesis after hatching of C. concholepas veliger larvae: Effect of sulfate in the synthesis of proteoglycans. Comp. Biochem & Physiol. 96B: 613 619.

Perelman, A., Abeijon, C., Hirschberg, C., Inestrosa, N.C. and Brandan, E. (1990)Differential association and distribution of acetyl and butyryl cholinesterases with different rat liver subcellular organelles. J. Biol. Chem. 265: 214 220.

González, M., Perelman, A., Fuentes, M E., Castilla, J.C., Labarca, R., Brandan, E., González Plaza, R., and Inestrosa, N.C. (1990) The neurotransmitter related enzyme acetylcholinesterase in juveniles of Concholepas concholepas (Mollusca; Gastropoda; Muricidae) J. Exp. Zool. 255: 1 8.

Andrade, W., and Brandan, E. (1991) Isolation and characte¬rization of rat skeletal muscle proteoglycan decorin and compari¬son with the human fibroblast decorin. Comp. Biochem. Physiol. 100: 565 570.

Brandan, E., Fuentes, M.E. and Andrade, W. (1991) The pro¬teoglycan decorin is synthesized and secreted by differentiated myotubes. Eur. J. Cell Biol. 55: 209 216.

Alvarez, J., Moreno, R., Llanos, O., Inestrosa, N.C., Brandan, E., Colby, T., and Esch, F. (1992). Axonal sprouting induced in the sciatic nerve by the amyloid precursor protein (APP) and other antiproteases. Neurosc. Lett. 144: 130 134.

Brandan, E., González, M., Inestrosa, N.C., Tremblay, C. and Urrea, R. (1992) A high molecular weight proteoglycan is diffe¬rentially expressed during development of the mollusc Concholepas concholepas. J. Exp. Zool. 264: 363 371.

González, R., Urrea, R., González, M., Inestrosa, N.C., and Brandan, E. (1992)Isolation of proteoglycans synthesized by rat heart. Evidence for the presence of several distinct forms. Gen. Pharmac. 23: 249 255.

Miquel, J.F., Rigotti, A., Rojas, E., Brandan, E., and Nervi, F. (1992) Isolation and purification of human biliary vesicles with potent cholesterol nucleation promoting activity. J. Clin. Scs. 82: 175 180.

Brandan, E., Fuentes, M.E., and Andrade, W. (1992) Decorin, a chondroitin/dermatan sulfate proteoglycan is under neural control in rat skeletal muscle. J. Neurosci. Res. 32: 51 59.

Urrea, R., González, M., Inestrosa, N.C. and Brandan, E. (1992) Sulfation is required for mobility of veliger larvae of Concholepas concholepas (Mollusca; Gastropoda; Muricidae). J. Exp. Zool. 261: 365 372.

Campos, A., Nuñez, R., Koenig, C.S. Carey, D.J., Brandan, E. (1993) A lipid anchored heparan sulfate proteoglycan is present in the surface of differentiated skeletal muscle cells: Isolation and biochemical characterization. Eur. J. Biochem. 216: 587-595.

Brandan, E., and Inestrosa, N.C. (1993) Extracellular matrix components and amyloid in neuritic plaques of the Alzheimer`s disease. Gen. Pharmacol. 24: 1063-1068

Brandan, E., Urrea, R., and Gajardo, G. (1993) Effect of salt concentration on the synthesis of sulfated macromolecules in the brine shrimp (Artemia franciscana): Changes of sulfation rate during development. Comp. Biochem. Physiol. 105A: 519-523.

Melo, F., and Brandan, E. (1993) Decorin is specifically solubilized by heparin from the extracellular matrix of rat skeletal muscles. FEBS Letts. 319: 249 252.

Miquel, J.F., Núñez, L., Rigotti, A., Amigo, L., Brandan, E., and Nervi, F. (1993) Isolation and partial characterization of cholesterol pronucleating hidrophobic glycoproteins associated with native biliary vesicles. FEBS Letts. 318: 45-49.

Koenig, C.S., Dabike, M., Núñez, R., Munizaga, A., Brandan, E., and Garrido, J. (1994)Differentiation of oxyntic cells and cell-matrix interactions during avian gastric gland morphogenesis. Biol Res 27: 177-192.

104. Brandan, E. (1994)Proteoglycans in skeletal muscles. (Invited review). Brazilian J. Med Biol Res . 27: 2109-2116.

Rodriguez, S.R., Riquelme, C., Campos, E.O., Chavez, P., Brandan, E., and Inestrosa, N.C. (1995) Behavorial responses of Concholepas concholepas (Bruguière, 1789) larvae to natural and artificial cues and microbial films. Biol. Bull. 189: 272-279.

Brandan, E; Campos, E; Rodriguez, S and Inestrosa, N. C. (1995) Extracellular matrix constituents induce larval settlement of concholepas concholepas. Segundo Congreso Ecuatoriano de Acuicultura. Eds. Calderón y Sorgeloos, CENAIM pp. 271-276.

Brandan, E., Melo, F., García, M. de A. and Contreras, M. (1996) Significantly reduced expression of the proteoglycan decorin in Alzheimer`s disease fibroblasts. J. Clin. Pathol: Mol. Pathol. 49: 351-356.

Brandan, E., Carey, D.J., Larraín, J., Melo, F., and Campos, A. (1996) Synthesis and processing of glypican during differentiation of skeletal muscle cells. Eur. J. Cell Biol. 71: 170-176.

Melo. F., Carey, D.J. and Brandan, E. (1996) Extracellular matrix is required for skeletal muscle differentiation but not myogenin expression. J. Cell Biochem. 62: 227-239.

Rudolph MI, García MA, Sepulveda M, Brandan, E., Reinicke K, Nicovani S, Villan L. (1997) Ethodin: pharmacological evidence of the interaction between smooth muscle and mast cells in the myometrium. J Pharmacol Exp Ther 282: 256-261.

Larraín, J., Cizmeci-Smith, G., Troncoso, V., Stahl, R.C., Carey, D.J. and Brandan, E. (1997)Syndecan-1 expression is downregulated during myoblasts terminal differentiation: Modulation by growth factors and retinoic acid. J. Biol. Chem. 272: 18418-18424.

Larraín, J., Alvarez, J., Hassell, J.R. and Brandan E. (1997) Expression of perlecan, a proteoglycan that binds myogenic inhibitory basic fibroblast growth factor, is down regulated during skeletal muscle differentiation. Exp. Cell Res. 234: 405-412.

Cáceres, J., and Brandan, E. (1997)Interaction between alzheimer`s disease A4 precursor protein (APP) and the extracellular matrix: evidence for a direct participation of heparan sulfate proteoglycans. J. Cell Biochem. 65: 145-158.

Larraín, J, Carey, D and Brandan, E. (1998) Syndecan-1 Expression Inhibits Myoblast Differentiation through a Basic Fibroblast Growth Factor-Dependent Mechanism. J. Biol. Chem. 273: 32288-32296.

Schönherr, E., Broszat, M., Brandan, E., Brucknur, P., and Kresse, H. (1998) Decorin core protein fragment Leu155-Val260 interacts with TGF- but does not compete for decorin binding to type I collagen. Arch. Biochem. Biophys. 355: 241-248.

Brandan, E., and Larraín, J. (1998) Heparan Sulfate Proteoglycans During Terminal Skeletal Muscle Cell Differentiation: Possible Functions And Regulation Of Their Expression. (Invited review) Basic and Applied Myology 8: 107-114.

Fuentealba, L., Carey, D.J, and Brandan, E. (1999) Antisense Inhibition of Syndecan-3 Expression During Skeletal Muscle Differentiation Accelerates Myogenesis Through A Basic Fibroblast Growth Factor-Dependent Mechanism. J. Biol. Chem. 274: 37876-37884.

Villar, MJ. Hassell, J., and Brandan, E. (1999) The interaction of skeletal muscle cells with collagen type iv is mediated by perlecan associated to the cell surface. J. Cell. Biochem. 75: 665-674.

Cáceres, S., Cuellar, C., Casar, J.C., Garrido, J., Schaefer, L., Kresse, H and Brandan, E. (2000) Synthesis of proteoglycans is augmented in dystrophic mdx mouse skeletal muscle. Eur. J. Cell Biol. 79: 173 – 181.

Olguin, H., and Brandan, E. (2001) Expression and localization of proteoglycans during limb myogenic activation. Dev. Dyn. 221: 106-115.

Riquelme, C., Larraín, J., Schönherr, E., Henríquez, J.P., Kresse, H and Brandan, E. (2001) Antisense Inhibition of Decorin Expression in Myoblasts Decreases Cell Responsiveness to Transforming Growth Factor and Accelerates Skeletal Muscle Differentiation. J. Biol. Chem. 276: 3589-3596.

Alvarez, K., Fadic, R and Brandan, E. (2002) Augmented synthesis and differential localization of heparan sulfate proteoglycans in Duchenne muscular dystrophy. J. Cell. Biochem. 85: 703-713.

Henriquez, J.P., Casar, J.C., Fuentealba, L., Carey, D.J. and Brandan, E. (2002) Extracellular matrix located histone H1 binds to perlecan in muscle cells and is present in regenerating muscle. J. Cell Sci. 115: 2041-2051.

Osses, N. and, E. Brandan (2002) ECM is required for skeletal muscle differentiation independently of muscle regulatory factor expression. Am. J. Phys. Cell. Phys. 282: C383-C394.

Olguin, H.C. Santander, C, and Brandan, E. (2003).Inhibition of myoblast migration via decorin expression is critical for normal skeletal muscle differentiation. Dev. Biol. 259: 209-224.

Lopez-Casillas F, Riquelme C, Perez-Kato Y, Ponce-Castaneda MV, Osses N, Esparza-Lopez J, Gonzalez-Nunez G, Cabello-Verrugio C, Mendoza V, Troncoso V, Brandan E. (2003). Betaglycan expression is transcriptionally up-regulated during skeletal muscle differentiation. Cloning of murine betaglycan gene promoter and its modulation by MyoD, retinoic acid, and transforming growth factor-beta. J. Biol. Chem 278: 382-90

Minniti, A., Labarca, M., Hurtado, C. and Brandan, E. (2004) Caenorhabditis elegans syndecan (SDN-1) associates with the nervous system and the vulva, and is required for normal egg laying. J. Cell Sci. 117: 5179-90.

Araya, R., Riquelme, C., Brandan, E and Saez, J.C. (2004) The formation of skeletal muscle myotubes requires functional membrane receptors activated by extracellular ATP. Brain Res. Rev. 47: 174-88.

Aldunate, R., Casar, J.C., Brandan, E and Inestrosa, N.C. (2004) Structural and Functional Organization of Synaptic Acetylcholinesterase. Brain Res. Rev. 47: 96-104

Casar, J.C., McKechnie, B.A., Fallon, J.R., Young, M.F. and Brandan, E. (2004) Transient Up-regulation of Biglycan During Skeletal Muscle Regeneration: Delayed Fiber Growth along with Decorin Increase in Biglycan-Deficient Mice. Dev. Biol. 268: 358-371

Casar, JC., Cabello, C., Olguín, H., Aldunate, R., Inestrosa, NC., and Brandan, E. (2004) Heparan sulfate proteoglycans are increased during skeletal muscle regeneration: requirement of syndecan-3 for successful fiber formation. J. Cell Sci. 117: 73-84

Villena, J and Brandan, E. (2004) Dermatan Sulfate Exerts an Enhanced Growth Factor Response on Skeletal Muscle Satellite Cell Proliferation and Migration. J. Cell. Physiol. 198: 169-178.

Moreno, M., Muñoz, R., Aroca, F., Labarca, M., Brandan, E. and Larraín, J. (2005) Biglycan is a new extracellular component of the Chordin-BMP4 signalling pathway. EMBO J. 24,:1397-1405.

Fadic, R., Mezzano, V., Alvarez, K., Cabrera, D., Holmgren, J. and Brandan, E. (2006).Increase in decorin and biglycan in Duchenne Muscular Dystrophy: role of fibroblasts as cell source of these proteoglycans in the disease. J Cell Mol Med 10:758-769

Droguett, R., Cabello-Verrugio, C., Riquelme, C. and Brandan, E. (2006) Extracellular proteoglycans modifies TGF-bio-availability attenuating its signaling during skeletal muscle differentiation. Matrix Biol. 25: 332-341

Brandan, E., Retamal, C., Cabello-Verrugio, C. and María-Paz Marzolo. (2006) The Low density lipoprotein receptor-related protein, LRP, functions as an endocytic receptor for decorin. J. Biol. Chem. 281: 31562-71

Ugarte, G. and Brandan, E. (2006) Transforming growth factor  signaling is regulated by electrical activity in skeletal muscle cells: TGF-β type I receptor is transcriptionally regulated by myotube excitability. J. Biol. Chem. 281: 18473-18481

Osses, N., Lopez-Rovira,, T., Ventura, F. and Brandan, E. (2006) Sulfation is required for Bone Morphogenetic Protein 2 dependent Id1 gene Induction but not for Early Transduction Signaling Events. Biochem. Biophys. Res. Comm. 344: 1207-15

Santander, C., and Brandan, E. (2006). Betaglycan induces TGF-β signaling in a ligand-independent manner, through activation of the p38 pathway. Cell. Signal. 18: 1482-1491

Gutierrez, J., Osses, N and Brandan, E. (2006) Changes in secreted and cell associated proteoglycan synthesis during conversion of myoblasts to osteoblasts in response to bone morphogenetitec protein type-2. J. Cell. Physiol. 206: 58-67

Mezzano, V., Cabrera, D., Vial, C. and Brandan, E. (2007) Constitutively Activated Dystrophic Muscle Fibroblasts Show a Paradoxical Response to TGF-β and CTGF/CCN2. J. Cell. Commun. Signal. 1: 205-17.

Cabello-Verrugio, C and Brandan, E. (2007) A Novel Modulatory Mechanism of TGF- Signaling through Decorin and LRP-1. J. Biol. Chem. 282: 18842-50

Cortés, V., Amigo, L, Donoso, K., Valencia, I., Quiñones, V., Zanlungo, S., Brandan, E and Rigotti, A. (2007) Adenovirus-mediated hepatic syndecan-1overexpression induces hepatocyte proliferationand hyperlipidaemia in mice. Liver Int. 27: 569-581

Brandan, E., Cabello-Verrugio, C. and Vial, C. (2008) Novel Regulatory Mechanisms for the Proteoglycans Decorin and Biglycan During Muscle Formation and Muscular Dystrophy. Matrix Biol. Invited Review. 27: 700-708

Nguyen TQ, Roestenberg P, van Nieuwenhoven FA, Bovenschen N, Li Z, Xu L, Oliver N, Aten J, Joles JA, Vial C, Brandan E, Lyons KM, Goldschmeding R. (2008) CTGF Inhibits BMP-7 Signaling in Diabetic Nephropathy. Am Soc Nephrol. 11: 2098-107.

Colombres M, Henríquez JP, Reig GF, Scheu J, Calderón R, Alvarez A, Brandan E, Inestrosa NC.(2008) Heparin activates Wnt signaling for neuronal morphogenesis. J Cell Physiol. 216: 805-15.

Vial, C., Zúñiga, L., Cabello-Verrugio, C., Cañón, P., Fadic, R. and Brandan, E. (2008) Skeletal muscle cells express the profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which induces their dedifferentiation. J. Cell. Physiol. 215: 410-21.

Osses, N., Casar, J.C. and Brandan, E (2009)Inhibition of Extracellular Matrix Assembly Induces the Expression of Osteogenic Markers in Skeletal Muscle Cells by a BMP-2 Independent Mechanism. BMC Cell Biology, 10:73.

Dropelmann, D., Gutierrez, J., Vial, C. and Brandan, E, (2009) MMP-2 deficient fibroblasts exhibit an alteration in the fibrotic response to CTGF/CCN2 due to increase in the levels of endogenous fibronectin. J. Biol. Chem. 284: 13551-13561.

Medina, W.T., Laurent, S., Brandan, E, and Aguilera, J.M. (2010) Uptake of tritiated liquids by individual breakfast cereal flakes. Journal of Food Science 375: 194-200.

Droguett, R. Cabello-Verrugio, C., Santander, C and Brandan, E. (2010) TGF- receptors, in a smad-independent manner, are required for terminal skeletal muscle differentiation. Exp. Cell Res. 316: 2487-2503.

Ugarte, G., Santander, C. and Brandan, E. (2010) Syndecan-4 and β1 Integrin are regulated by electrical activity in skeletal muscle: implications on cell adhesion. Matrix Biol. 29, 383-92.

Gutierrez, J. and Brandan, E. (2010) A Novel Mechanism of Sequestering FGF-2 by Glypican in Lipid Rafts, Allowing Skeletal Muscle Differentiation. Mol. Cell. Biol. 30: 1634-1649. Plus Cover Photograph.

Morales MG, Cabello-Verrugio C, Santander C, Cabrera D, Goldschmeding R, Brandan E. (2011)Overexpression of Connective Tissue Growth Factor in Skeletal Muscle Induces Damage, Fibrotic Response and a Decrease in Muscular Strength. J. Pathol. 225: 490-501

Cabello-Verrugio, C., Acuña, M.J., Morales, M.G., Becerra, A., Simon, F., and Brandan, E. (2011) Fibrotic response induced by angiotensin-II requires NAD(P)H oxidase-induced reactive oxygen species (ROS) in skeletal muscle cells. Biochem. Biophys. Res. Com. 410: 665-70.

Vial, C., Gutiérrez, J., Santander, C., Cabrera, D., and Brandan, E. (2011) Decorin interacts with CTGF/CCN2 through LRR12 inhibiting its biological activity. J. Biol. Chem. 286: 24242-24252.

Cabello-Verrugio, C., Córdova, G., Vial, C., Zúñiga, L., and Brandan, E. (2011). Connective Tissue Growth Factor induction by lysophosphatidic acid requires transactivation of Transforming Growth Factor Type  receptors and the JNK pathway. Cell. Signal. 23: 449-457.

Morales, G., Vazquez, Y., Acuña, MJ., Rivera, JC., Simon, F., Salas, JD., Álvarez Ruf, J., Brandan, E., Cabello-Verrugio, C. (2012) Angiotensin II-induced profibrotic effects require p38MAPK activity and transforming growth factor beta 1 expression in skeletal muscle cells. Int. J. Biochem. Cell Biol. 44: 1993– 2002

Cabello-Verrugio, C., Morales, G, Cabrera, D and Brandan, E. (2012)Angiotensin II receptor type 1 blockade decreases CTGF/CCN2-mediated damage and fibrosis in skeletal muscle. J. Cell. Mol. Med. 16, 752-64

Cabello-Verrugio, C., Cofré, C., Santander, C., Melo, F. and Brandan, E. (2012) The Internal Region Leucine-rich Repeat 6 of Decorin Interacts with LRP-1, Modulates TGFDependent Signaling and inhibits TGF- Dependent Fibrotic Response in Skeletal Muscles. J Biol Chem 287: 6773-87

Morales MG, Gutierrez J, Cabello-Verrugio C, Cabrera D, Lipson KE, Goldschmeding R, Brandan E. (2013). Reducing CTGF/CCN2 slows down mdx muscle dystrophy and improves cell therapy. Hum Mol Genet. 15: 4938-512.

Morales, G., Cabrera, D., Céspedes, C., Vio, C., Vázquez, Y., Brandan, E., and Cabello-Verrugio, C. (2013). Inhibition of angiotensin-converting enzyme decreases skeletal muscle fibrosis in dystrophic mice by a diminution on the expression and activity of connective tissue growth factor (CTGF/CCN-2) Cell Tiss Res 353: 173-87.

Brandan, E and Gutierrez, J. (2013) Role of skeletal muscle proteoglycans during myogenesis. (Invited Review) Matrix Biol. 32: 289–297

Brandan, E and Gutierrez, J. (2013) Role of proteoglycans in the regulation of skeletal muscle fibrotic response. (Invited Review). FEBS J. 280: 4109–4117

Painemal P, Acuña MJ, Riquelme C, Brandan E, Cabello-Verrugio C. (2013) Transforming growth factor type beta 1 increases the expression of angiotensin II receptor type 2 by a SMAD- and p38 MAPK-dependent mechanism in skeletal muscle. Biofactors, 39: 467-75

Calligaris, SD., Lecanda, M., Solis, F., Ezquer, M., Gutiérrez, J., Brandan, E., Leiva, A., Sobrevia, L., Conget, P. (2013) Mice Long-Term High-Fat Diet Feeding Recapitulates Human Cardiovascular Alterations: An Animal Model to Study the Early Phases of Diabetic Cardiomyopathy. Plos.One 8(4):e60931

Meneses, C., Morales, M.G., Abrigo, J., Simon, F., Brandan, E. and Cabello-Verrugio, C. (2014). The angiotensin (1-7)/Mas axis reduces myonuclear apoptosis during recovery from angiotensin II-induced skeletal muscle atrophy in mice. Pflug. Arch. Eur. J. Phy. 467: 1975-84.

Pessina, P., Cabrera, D., Morales, MG., Riquelme, CA., Gutiérrez, J., Serrano, AL., Brandan, E. and Muñoz-Cánoves, P. (2014) Novel and optimized strategies for inducing fibrosis in vivo: focus on Duchenne Muscular Dystrophy. Skeletal Muscle, 4:7.

Riquelme, CA., Acuña, MJ., Torrejón, J., Rebolledo, D., Cabrera, D., Santos, RA. and Brandan, E. (2014) . ACE2 is augmented in dystrophic skeletal muscle and plays a role in decreasing associated fibrosis. PLoS One 2;9(4):e93449. doi: 10.1371

Cabrera, D., Gutiérrez, J. Cabello-Verrugio, C., Morales, M.G., Mezzano, S., Fadic, R., Casar, JC., Hancke, J., and Brandan, E. (2014) Andrographolide attenuates skeletal muscle dystrophy in mdx mice and increases efficiency of cell therapy by reducing fibrosis. Skeletal Muscle 4:6.

Gutiérrez, J., Cabrera, D., and Brandan, E. (2014) Glypican-1 regulates myoblast response to HGF via met in a lipid raft-dependent mechanism: Effect on migration of skeletal muscle precursor cells. Skeletal Muscle 12;4(1):5. doi: 10.1186/2044-5040-4-5.

Acuña MJ, Pessina P, Olguin H, Cabrera D, Vio CP, Bader M, Muñoz-Canoves P, Santos RA, Cabello-Verrugio C, Brandan E. (2014). Restoration of muscle strength in dystrophic muscle by angiotensin-1-7 through inhibition of TGF-β signalling. Hum Mol Genet. 23: 1237-49

Cisternas, P., Henríquez, J.P., Brandan, E. and Inestrosa, NC. (2014) Wnt signaling in skeletal muscle dynamics: myogenesis, neuromuscular synapse and fibrosis. Mol. Neurobiol. 49: 574-89.

Gutiérrez, J., Droppelmann, CA., Contreras, O., Takahashi, C., and Brandan, E. (2015) RECK-mediated β1-integrin regulation by TGF-β1 is critical for wound contraction in mice. PLoS One 10(8):e0135005.

Brandan, E. (2015) Heparan sulfate provides a mechanism to respond to FGFR2b and control regenerative expansion. J Cell Commun Signal. 9: 89.

Passos-Silva, D., Brandan, E. and Souza Santos, RA. (2015) Angiotensins as therapeutic targets beyond heart disease. Trends Pharmacol. Sci. 36: 310-320.

Cofre, C., Acuña, M.J., Contreras, O., Morales, M.G., Riquelme, CA., Cabello-Verrugio, C. and Brandan, E. (2015)Transforming growth factor type-β inhibits Mas receptor expression in fibroblasts but not in myoblasts or differentiated myotubes; Relevance to fibrosis associated to muscular dystrophies. BioFactors 41: 111-20.

Cordova, G., Rochard, A., Riquelme-Guzmán, C., Cofré, C., Scherman, D.,Bigey, P., and Brandan, E. (2015) SMAD3 and SP1/SP3 transcription factors collaborate to regulate Connective Tissue Growth Factor gene expression in myoblasts in response to Transforming Growth Factor β. J. Cell. Biochem. 116: 1880-7.

Cisternas, F., Morales, M.G., Meneses, C., Dimon, F., Brandan, E., Abrigo, J, Vazquez Y and Cabello-Verrugio, C. (2015) Angiotensin 1-7 Decreases Skeletal Muscle Atrophy induced by Angiotensin II through Mas Receptor Dependent Mechanism. Clin Sci. (Lond) 128: 307-19

Cabrera, D., Ruiz, A., Cabello-Verrugio, C., Brandan, E., Estrada, L., Pizarro, M., Solis, N., Torres, J., Barrera, F., and Arrese, M. (2016) Diet-Induced Nonalcoholic Fatty Liver Disease Is Associated with Sarcopenia and Decreased Serum Insulin-Like Growth Factor-1. Dig. Dis. Sci. DOI 10.1007/s10620-016-4285-0

Morales, M.G., Abrigo, J., Acuña, M.J., Santos, R., Bader, M, Brandan, E, Simon, F., Olgin, H., Cabrera, D. and Cabello-Verrugio, C. (2016). Ang 1-7 decreases muscle wasting by disuse. Dis Model Mech 9: 441-449.

Contreras, O., Rebolledo, D.L. Oyarzún, J.E., Olguín, H. and Brandan, E. (2016) Connective tissue cells expressing fibro/adipogenic progenitors markers increase under chronic damage; Relevance to fibroblast-myofibroblast differentiation and skeletal muscle fibrosis. Cell Tissue Res. 364: 647-60.

Fuenzalida, M., Espinoza, C., Pérez, M.A. Tapia-Rojas, Ch., Cuitino, L., Brandan, E. Inestrosa, N.C. (2016) Wnt signaling pathway improves central inhibitory synaptic transmission in a mouse model of Duchenne muscular dystrophy. Neurobiol. Dis. 86: 109-20.

Acuña, MJ., Salas, D., Cordova-Casanova, A., Cruz-Soca, A., Céspedes, C, Vío, C.P. and Brandan, E (2017) Blockade of Bradykinin receptors worsens the dystrophic phenotype of mdx mice: differential effects for B1 and B2 receptors. J Cell Commun Signal. doi: 10.1007/s12079-017-0439-x

Gonzalez, D., Contreras, O., Rebolledo, DL., Espinoza, JP., van Zundert, B., Brandan E. (2017) ALS skeletal muscle shows enhanced TGF-β signaling, fibrosis and induction of fibro/adipogenic progenitor markers. PLoS One 16;12(5):e0177649. doi:10.1371/journal.pone.0177649.

Cabrera, D., Wree, A., Povero, D., Solis, N., Hernandez, A., Pizarro, A, Moshage, H., Torres, J., Feldstein, A., Cabello-Verrugio, C., Brandan, E., Barrera, F., Arab, J. Arrese, M. (2017) Andrographolide ameliorates inflammation and fibrogenesis and attenuates inflammasome activation in experimental non-alcoholic steatohepatitis. Sci Rep. 14, 7(1):349.1doi: 10.1038/s41598-017-03675-z.

Contreras O, Brandan E. (2017) Fibro/adipogenic progenitors safeguard themselves: a novel mechanism to reduce fibrosis is discovered. J Cell Commun Signal. 11: 77-78.

Gonzalez, D., Rebolledo, D.L., Correa, L.M., Court, F., Cerpa, W., Lipson, K.E. Zundert, B.V. and Brandan, E. (2018) The inhibition of CTGF/CCN2 activity improves muscle and locomotor function in a murine ALS model. Hum. Mol. Gen. 27: 2913-2926

Contreras, O., Villarreal, M. and Brandan, E. (2018) Nilotinib impairs skeletal myogenesis by increasing myoblast proliferation. Skeletal Muscle 20, 8(1):5. doi: 10.1186/s13395-018-0150-5

Riquelme-Guzmán, C., Contreras, O., and Brandan E. (2018) Expression of CTGF/CCN2 in response to LPA is stimulated by fibrotic extracellular matrix via the integrin/FAK axis. Am. J. Physiol. Cell Physiol. 314: C415–C427.

Morales, M.G., Acuña, M.J., Cabrera, D., Goldschmeding, R and and Brandan E. (2018) The profibrotic connective tissue growth factor (CTGF/CCN2) correlates with the number of necrotic-regenerative foci in dystrophic muscle. J Cell Commun Signal. 12: 413-421.

Valle-Tenney R, Rebolledo D, Lipson KE, Brandan E. (2019)Role of hypoxia in skeletal muscle fibrosis: Synergism between hypoxia and TGF-β signaling upregulates CCN2/CTGF expression specifically in muscle fibers. Matrix Biol. 87: 48-65.

Contreras, O., Cruz-Soca, M., Theret, M., Soliman, H., Groppa, H., Wei, L., Rossi, F.M., and Brandan, E. (2019) TGF-β and PDGFRα signaling pathways cross-talk regulates stromal fibro/adipogenic progenitors’ differentiation. J. Cell Sci doi: 10.1242/jcs.232157

Contreras, O., Rossi, F.M., and Brandan, E. (2019) Adherent muscle connective tissue fibroblasts are phenotypically and biochemically equivalent to stromal fibro/adipogenic progenitors. Matrix Biol Plus

Rebolledo, D.L., González, D., Faundez-Contreras, J., Contreras, O., Murphy-Ullrich, J.E., Lipson, K.E. and Brandan, E. (2019) CTGF/CCN2 Modulates Denervation-induced Skeletal Muscle Fibrosis independently of TGF- Matrix Biol. doi: 10.1016/j.matbio.2019.01.002

Gonzalez, D and Brandan, E (2019) CTGF/CCN2 from skeletal muscle to nervous system: impact on neurodegenerative diseases. Mol. Neurobiol. In Press

Valle-Tenney R, Rebolledo D, Acuña MJ, Brandan E. (2020) HIF-hypoxia signaling in skeletal muscle physiology and fibrosis. J Cell Commun Signal. 14:147-158.

J Cell Sci. doi: 10.1242/jcs.242297J Cell Sci. doi: 10.1242/jcs.242297

Contreras, O., Soliman, H., Theret, M., Soliman, H., Groppa, E., Tung, L.W. Rossi, F.M., and Brandan, E. (2020) TGF-β signaling suppresses the expression of the Wnt transcription factor TCF7L2 and compromises TCF7L2-dependent functions in tissue-resident PDGFRa+ fibroblasts.

Contreras, O., Soliman, H., Theret, M., Rossi, F.M., and Brandan, E. (2020) TGF-b-driven downregulation of the Wnt/b-Catenin transcription factor TCF7L2/TCF4 in PDGFRa+ fibroblasts. J. Cell Sci. 133(12):jcs242297. doi: 10.1242/jcs.242297

Valle-Tenney R, Rebolledo D, Acuña MJ, Brandan E. (2020) HIF-hypoxia signaling in skeletal muscle physiology and fibrosis. J Cell Commun Signal. 14: 147-158.

Rebolledo, D.L., Acuña, M.J. and Brandan, E. (2021) Role of matricellular CCN proteins in skeletal muscle: Focus on CCN2/CTGF and its regulation by vasoactive peptides. Int J Mol Sci. 22, doi: 10.3390/ijms22105234

Contreras, O., Cordova-Casanova, A. and Brandan, E. (2021) PDGF-PDGFR Network Differentially Regulates Myogenic Cell Fate, Migration, Proliferation, and Cell Cycle Progression. Cell Signal, doi: 10.1016/j.cellsig.2021.110036

Gutiérrez, J., Gonzalez, D., Escalona, R., Takahashi, C., and Brandan, E. (2021) Reduced RECK levels accelerate skeletal muscle differentiation, improve muscle regeneration and decrease fibrosis. Faseb J. doi: 10.1096/fj.202001646RR

Gallardo, F.S., Córdova-Casanova, A., and Brandan, E. (2021) The Linkage Between Inflammation and Fibrosis in Muscular Dystrophies: The Axis Autotaxin-Lysophosphatidic Acid as a New Therapeutic Target? J. Cell Commun. Signal.

Rebolledo, D., Lipson, KE, and Brandan, E. (2021) Driving Fibrosis in Neuromuscular Diseases: Role and Regulation of Connective Tissue Growth Factor (CCN2/CTGF). Matrix Biol Plus

Córdova-Casanova, A., Cruz-Soca, M., Chun, J., Casar, J.C. and Brandan, E. (2022) Activation of the ATX/LPA/LPARs axis induces a fibrotic response in skeletal muscle. Matrix Biol. 109:121-139

Principal investigator

Enrique Brandan