Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Nov;76(21):4179-4201.
doi: 10.1007/s00018-019-03212-3. Epub 2019 Sep 28.

Molecular determinants of mesenchymal cell activation in fibroproliferative diseases

Loka R Penke  1 , Marc Peters-Golden  2
Affiliations
Review

Molecular determinants of mesenchymal cell activation in fibroproliferative diseases

Loka R Penke et al. Cell Mol Life Sci. 2019 Nov.

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.

Keywords: Apoptosis; De-differentiation; Differentiation proliferation; Fibroblast; Fibroproliferative diseases; Myofibroblast; Signaling pathways.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
A variety of extrinsic factors can damage healthy tissue, resulting in epithelial cell death/apoptosis, local inflammation, and activation of mesenchymal cells (e.g., Fibs). Under physiological conditions, homeostatic repair processes restore healthy tissue. When repair processes fail, Fibs/MFibs become aberrantly and persistently activated, leading to deposition of excess ECM and impaired tissue function
Fig. 2
Fig. 2
Schematic representation of well-characterized Fib activation signaling pathways and their crosstalk
Fig. 3
Fig. 3
Schematic representation of Fib differentiation and possible phenotypic fates during the process of de-differentiation
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214:199–210. doi: 10.1002/path.2277. - DOI - PMC - PubMed
    1. Gao B, Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology. 2011;141:1572–1585. doi: 10.1053/j.gastro.2011.09.002. - DOI - PMC - PubMed
    1. Straub JM, New J, Hamilton CD, Lominska C, Shnayder Y, Thomas SM. Radiation-induced fibrosis: mechanisms and implications for therapy. J Cancer Res Clin Oncol. 2015;141:1985–1994. doi: 10.1007/s00432-015-1974-6. - DOI - PMC - PubMed
    1. Mossman BT, Churg A. Mechanisms in the pathogenesis of asbestosis and silicosis. Am J Respir Crit Care Med. 1998;157:1666–1680. doi: 10.1164/ajrccm.157.5.9707141. - DOI - PubMed
    1. Ringehan Marc, McKeating Jane A., Protzer Ulrike. Viral hepatitis and liver cancer. Philosophical Transactions of the Royal Society B: Biological Sciences. 2017;372(1732):20160274. doi: 10.1098/rstb.2016.0274. - DOI - PMC - PubMed

Substances

LinkOut - more resources