title: Recent developments in myofibroblast biology: paradigms for connective tissue remodeling.
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.
authors.affiliation: Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada. boris.hinz@utoronto.ca
authors.forename: Boris
authors.initials: B
authors.lastname: Hinz
authors.forename: Sem H
authors.initials: SH
authors.lastname: Phan
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Thannickal
authors.forename: Marco
authors.initials: M
authors.lastname: Prunotto
authors.forename: Alexis
authors.initials: A
authors.lastname: Desmoulière
authors.forename: John
authors.initials: J
authors.lastname: Varga
authors.forename: Olivier
authors.initials: O
authors.lastname: De Wever
authors.forename: Marc
authors.initials: M
authors.lastname: Mareel
authors.forename: Giulio
authors.initials: G
authors.lastname: Gabbiani
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D003238:Connective Tissue / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000502:physiology; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D058628:Myofibroblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D059016:Tumor Microenvironment / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
chemical_list: D000199:Actins