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Myofibroblast differentiation and survival in fibrotic disease

Published online by Cambridge University Press:  23 August 2011

Kornelia Kis ,
Xiaoqiu Liu  and
James S. Hagood
Kornelia Kis
Affiliation:
Department of Pediatrics, Division of Respiratory Medicine, University of California-San Diego, San Diego, CA, USA
Xiaoqiu Liu
Affiliation:
Department of Pediatrics, Division of Respiratory Medicine, University of California-San Diego, San Diego, CA, USA
James S. Hagood*
Affiliation:
Department of Pediatrics, Division of Respiratory Medicine, University of California-San Diego, San Diego, CA, USA Rady Children's Hospital of San Diego, San Diego, CA, USA
*
*Corresponding author: James S. Hagood, University of California-San Diego, 9500 Gilman Drive, MC 0731, San Diego, CA 92093-0731. E-mail: jhagood@ucsd.edu
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Abstract

During wound healing, contractile fibroblasts called myofibroblasts regulate the formation and contraction of granulation tissue; however, pathological and persistent myofibroblast activation, which occurs in hypertrophic scars or tissue fibrosis, results in a loss of function. Many reviews outline the cellular and molecular features of myofibroblasts and their roles in a variety of diseases. This review focuses on the origins of myofibroblasts and the factors that control their differentiation and prolonged survival in fibrotic tissues. Pulmonary fibrosis is used to illustrate many key points, but examples from other tissues and models are also included. Myofibroblasts originate mostly from tissue-resident fibroblasts, and also from epithelial and endothelial cells or other mesenchymal precursors. Their differentiation is influenced by cytokines, growth factors, extracellular matrix composition and stiffness, and cell surface molecules such as proteoglycans and THY1, among other factors. Many of these effects are modulated by cell contraction. Myofibroblasts resist programmed cell death, which promotes their accumulation in fibrotic tissues. The cause of resistance to apoptosis in myofibroblasts is under ongoing investigation, but many of the same stimuli that regulate their differentiation are involved. The contributions of oxidative stress, the WNT–β-catenin pathway and PPARγ to myofibroblast differentiation and survival are increasingly appreciated.

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Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 13 , March 2011 , e27
Copyright
Copyright © Cambridge University Press 2011

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Further reading, resources and contacts

Hinz, B. (2007) Formation and function of the myofibroblast during tissue repair. Journal of Investigative Dermatology 127, 526-537Google Scholar
Hinz, B. (2010) The myofibroblast: paradigm for a mechanically active cell. Journal of Biomechanics 43, 146-155CrossRefGoogle ScholarPubMed
Wipff, P.-J. et al. (2007) Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix. Journal of Cell Biology 179, 1311-1323Google Scholar
Kisseleva, T. et al. (2011) Is it the end of the line for the EMT? Hepatology 53, 1433-1435 (Ref. 169).Google Scholar
A well-maintained website with excellent figures and movies, brief reviews, and helpful external links can be found at:http://www.cellmigration.org/.Google Scholar
Website of the American Society for Matrix Biology, with meeting announcements, resources and external links:http://www.asmb.net/.Google Scholar
Hinz, B. (2007) Formation and function of the myofibroblast during tissue repair. Journal of Investigative Dermatology 127, 526-537Google Scholar
Hinz, B. (2010) The myofibroblast: paradigm for a mechanically active cell. Journal of Biomechanics 43, 146-155CrossRefGoogle ScholarPubMed
Wipff, P.-J. et al. (2007) Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix. Journal of Cell Biology 179, 1311-1323Google Scholar
Kisseleva, T. et al. (2011) Is it the end of the line for the EMT? Hepatology 53, 1433-1435 (Ref. 169).Google Scholar
A well-maintained website with excellent figures and movies, brief reviews, and helpful external links can be found at:http://www.cellmigration.org/.Google Scholar
Website of the American Society for Matrix Biology, with meeting announcements, resources and external links:http://www.asmb.net/.Google Scholar