Reversible differentiation of myofibroblasts by MyoD

Louise Hecker, Rajesh Jagirdar, Toni Jin, Victor J. Thannickal

Research output: Contribution to journalArticle

64 Citations (Scopus)

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-?1 (TGF-?1). 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-?1/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.

Original languageEnglish (US)
Pages (from-to)1914-1921
Number of pages8
JournalExperimental Cell Research
Volume317
Issue number13
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

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Myofibroblasts
Transforming Growth Factors
Mitogens

Keywords

  • De-differentiation
  • Fibroblasts
  • Fibrosis
  • MyoD
  • Tissue repair

ASJC Scopus subject areas

  • Cell Biology

Cite this

Reversible differentiation of myofibroblasts by MyoD. / Hecker, Louise; Jagirdar, Rajesh; Jin, Toni; Thannickal, Victor J.

In: Experimental Cell Research, Vol. 317, No. 13, 01.08.2011, p. 1914-1921.

Research output: Contribution to journalArticle

Hecker, Louise ; Jagirdar, Rajesh ; Jin, Toni ; Thannickal, Victor J. / Reversible differentiation of myofibroblasts by MyoD. In: Experimental Cell Research. 2011 ; Vol. 317, No. 13. pp. 1914-1921.
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