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PMID: 22387320 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Recent developments in myofibroblast biology: paradigms for connective tissue remodeling.

The American journal of pathology ·Vol. 180 ·No. 4 ·2012-04-00 ·Pages 1340-55

Hinz B, Phan SH, Thannickal VJ, Prunotto M, Desmoulière A, Varga J, De Wever O, Mareel M, Gabbiani G

Abstract

The discovery of the myofibroblast has opened new perspectives for the comprehension of the biological mechanisms involved in wound healing and fibrotic diseases. In recent years, many advances have been made in understanding important aspects of myofibroblast basic biological characteristics. This review summarizes such advances in several fields, such as the following: i) force production by the myofibroblast and mechanisms of connective tissue remodeling; ii) factors controlling the expression of α-smooth muscle actin, the most used marker of myofibroblastic phenotype and, more important, involved in force generation by the myofibroblast; and iii) factors affecting genesis of the myofibroblast and its differentiation from precursor cells, in particular epigenetic factors, such as DNA methylation, microRNAs, and histone modification. We also review the origin and the specific features of the myofibroblast in diverse fibrotic lesions, such as systemic sclerosis; kidney, liver, and lung fibrosis; and the stromal reaction to certain epithelial tumors. Finally, we summarize the emerging strategies for influencing myofibroblast behavior in vitro and in vivo, with the ultimate goal of an effective therapeutic approach for myofibroblast-dependent diseases.

MeSH Terms
Actins/genetics,metabolism Animals Cell Differentiation/physiology Connective Tissue/physiology Epigenesis, Genetic/physiology Fibrosis Gene Expression Regulation/physiology Humans Myofibroblasts/cytology,metabolism,physiology Tumor Microenvironment/physiology Wound Healing/physiology
Chemicals
Actins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Hinz Boris
Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada. [email protected]
Phan Sem H
Thannickal Victor J
Prunotto Marco
Desmoulière Alexis
Varga John
De Wever Olivier
Mareel Marc
Gabbiani Giulio
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
1525-2191
DOI
10.1016/j.ajpath.2012.02.004
Email
[email protected]
Published
2012-04-00
Epub
2012-00-02
Pages
1340-55
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC3640252
Subset
IM
Grants
CIHR · 219974 · Canada
NIAMS NIH HHS · R01 AR042309 · United States
NHLBI NIH HHS · R01 HL094230 · United States
NHLBI NIH HHS · R01 HL052285 · United States
NHLBI NIH HHS · HL-091775 · United States
NHLBI NIH HHS · HL-094230 · United States
NHLBI NIH HHS · P01 HL091775 · United States
NHLBI NIH HHS · R01 HL028737 · United States
NHLBI NIH HHS · HL-067967 · United States
NHLBI NIH HHS · HL-028737 · United States
NHLBI NIH HHS · P01 HL031963 · United States
NHLBI NIH HHS · R37 HL028737 · United States
NHLBI NIH HHS · R01 HL067967 · United States
CIHR · 1004005 · Canada
NHLBI NIH HHS · HL-031963 · United States
CIHR · 210820 · Canada
NHLBI NIH HHS · HL-052285 · United States
External Links
PubMed source DOI: 10.1016/j.ajpath.2012.02.004 PMC Full Text View journal details
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