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Molecular determinants of mesenchymal cell activation in fibroproliferative diseases

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Abstract

Uncontrolled scarring, or fibrosis, can interfere with the normal function of virtually all tissues of the body, ultimately leading to organ failure and death. Fibrotic diseases represent a major cause of death in industrialized countries. Unfortunately, no curative treatments for these conditions are yet available, highlighting the critical need for a better fundamental understanding of molecular mechanisms that may be therapeutically tractable. The ultimate indispensable effector cells responsible for deposition of extracellular matrix proteins that comprise scars are mesenchymal cells, namely fibroblasts and myofibroblasts. In this review, we focus on the biology of these cells and the molecular mechanisms that regulate their pertinent functions. We discuss key pro-fibrotic mediators, signaling pathways, and transcription factors that dictate their activation and persistence. Because of their possible clinical and therapeutic relevance, we also consider potential brakes on mesenchymal cell activation and cellular processes that may facilitate myofibroblast clearance from fibrotic tissue—topics that have in general been understudied.

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Acknowledgements

This work was supported by NIH Grant HL094311 (to MPG) and an American Heart Association Fellowship Award (to LRP),

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  1. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, 6301 MSRB III, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109-5642, USA

    Loka R. Penke & Marc Peters-Golden

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Correspondence to Marc Peters-Golden.

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Penke, L.R., Peters-Golden, M. Molecular determinants of mesenchymal cell activation in fibroproliferative diseases. Cell. Mol. Life Sci. 76, 4179–4201 (2019). https://doi.org/10.1007/s00018-019-03212-3

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  • DOI: https://doi.org/10.1007/s00018-019-03212-3

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