Review
Recent Developments in Myofibroblast Biology: Paradigms for Connective Tissue Remodeling

https://doi.org/10.1016/j.ajpath.2012.02.004Get rights and content
Under a Creative Commons license
open access

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.

Cited by (0)

Supported by grants from the Canadian Institutes of Health Research (210820 and 219974 to B.H.), a grant from the Collaborative Health Research Program Natural Sciences and Engineering Research Council of Canada/Canadian Institutes of Health Research (1004005), a grant from the Heart and Stroke Foundation Ontario (NA7086 to B.H.), a grant from the Swiss National Science Foundation (3200-067254 to B.H.), grants from the NIH (HL-028737, HL-031963, HL-052285, and HL-091775 to S.H.P.; HL-067967 and HL-094230 to V.J.T.), grants from the University of Limoges and from the French Ministry of Research (A.D.), AR42309 (J.V.), grants from the Flemish League Against Cancer, Foundation Against Cancer, and the Fund for Scientific Research-Flanders (O.D.W. and M.M.).