Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 180, Issue 4, Pages 1340-1355Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2012.02.004
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Funding
- Canadian Institutes of Health Research [210820, 219974]
- Natural Sciences and Engineering Research Council of Canada/Canadian Institutes of Health Research [1004005]
- Heart and Stroke Foundation Ontario [NA7086]
- Swiss National Science Foundation [3200-067254]
- NIH [HL-028737, HL-031963, HL-052285, HL-091775, HL-067967, HL-094230]
- University of Limoges
- French Ministry of Research [AR42309]
- Flemish League Against Cancer, Foundation Against Cancer
- Fund for Scientific Research-Flanders
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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; factors controlling the expression of alpha-smooth muscle actin, the most used marker of myofibroblastic phenotype and, more important, involved in force generation by the myofibroblast; and 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. (Ant J Pathol 2012, 180: 1340-1355; DOI: 10.1016/j.ajpath.2012.02.004)
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