title: Reversible differentiation of myofibroblasts by MyoD.
abstract: Myofibroblasts participate in tissue repair processes in diverse mammalian organ systems. The deactivation of myofibroblasts is critical for termination of the reparative response and restoration of tissue structure and function. The current paradigm on normal tissue repair is the apoptotic clearance of terminally differentiated myofibroblasts; while, the accumulation of activated myofibroblasts is associated with progressive human fibrotic disorders. The capacity of myofibroblasts to undergo de-differentiation as a potential mechanism for myofibroblast deactivation has not been examined. In this report, we have uncovered a role for MyoD in the induction of myofibroblast differentiation by transforming growth factor-β1 (TGF-β1). Myofibroblasts demonstrate the capacity for de-differentiation and proliferation by modulation of endogenous levels of MyoD. We propose a model of reciprocal signaling between TGF-β1/ALK5/MyoD and mitogen(s)/ERK-MAPK/CDKs that regulate myofibroblast differentiation and de-differentiation, respectively. Our studies provide the first evidence for MyoD in controlling myofibroblast activation and deactivation. Restricted capacity for de-differentiation of myofibroblasts may underlie the progressive nature of recalcitrant human fibrotic disorders.
authors: Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, 1530 3rd Avenue South, Birmingham, AL 35294, USA
authors: Louise
authors: L
authors: Hecker
authors: Rajesh
authors: R
authors: Jagirdar
authors: Toni
authors: T
authors: Jin
authors: Victor J
authors: VJ
authors: Thannickal
mesh_terms: D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D017570:MyoD Protein / Q000378:metabolism*; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D053773:Transforming Growth Factor beta1