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Myofibroblast dedifferentiation proceeds via distinct transcriptomic and phenotypic transitions.

ABSTRACT: Myofibroblasts are the major cellular source of collagen, and their accumulation - via differentiation from fibroblasts and resistance to apoptosis - is a hallmark of tissue fibrosis. Clearance of myofibroblasts by dedifferentiation and restoration of apoptosis sensitivity has the potential to reverse fibrosis. Prostaglandin E2 (PGE2) and mitogens such as FGF2 have each been shown to dedifferentiate myofibroblasts, but - to our knowledge - the resultant cellular phenotypes have neither been comprehensively characterized or compared. Here, we show that PGE2 elicited dedifferentiation of human lung myofibroblasts via cAMP/PKA, while FGF2 utilized MEK/ERK. The 2 mediators yielded transitional cells with distinct transcriptomes, with FGF2 promoting but PGE2 inhibiting proliferation and survival. The gene expression pattern in fibroblasts isolated from the lungs of mice undergoing resolution of experimental fibrosis resembled that of myofibroblasts treated with PGE2 in vitro. We conclude that myofibroblast dedifferentiation can proceed via distinct programs exemplified by treatment with PGE2 and FGF2, with dedifferentiation occurring in vivo most closely resembling the former.

SUBMITTER: Fortier SM

PROVIDER: S-EPMC8026183 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Myofibroblast de-differentiation proceeds via distinct transcriptomic and phenotypic transitions

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-03-23 | GSE163832 | GEO

Myofibroblast de-differentiation proceeds via distinct transcriptomic and phenotypic transitions [RNA-Seq]

Project description:Myofibroblasts are the major cellular source of collagen, and their accumulation – via differentiation from fibroblasts and resistance to apoptosis – is a hallmark of tissue fibrosis. Clearance of myofibroblasts by de-differentiation and restoration of apoptosis sensitivity has the potential to reverse fibrosis. Prostaglandin E2 (PGE2) and mitogens such as fibroblast growth factor-2 (FGF2) have each been shown to de-differentiate myofibroblasts, but the resultant cellular phenotypes have neither been comprehensively characterized nor compared. Here we show that PGE2 elicited de-differentiation of human lung myofibroblasts via cAMP/PKA while FGF2 utilized MEK/ERK. The two mediators yielded transitional cells with distinct transcriptomes, with FGF2 promoting but PGE2 inhibiting proliferation and survival. The gene expression pattern in fibroblasts isolated from the lungs of mice undergoing resolution of experimental fibrosis resembled that of myofibroblasts treated with PGE2 in vitro. We conclude that myofibroblast de-differentiation can proceed via distinct programs exemplified by treatment with PGE2 and FGF2, with that occurring in vivo most closely resembling the former.

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Myofibroblast de-differentiation proceeds via distinct transcriptomic and phenotypic transitions [miRNA-Seq]

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Myofibroblast de-differentiation proceeds via distinct transcriptomic and phenotypic transitions

Project description:Myofibroblast de-differentiation proceeds via distinct transcriptomic and phenotypic transitions

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Myofibroblast de-differentiation proceeds via distinct transcriptomic and phenotypic transitions [miRNA-Seq]

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Impaired Myofibroblast Dedifferentiation Contributes to Nonresolving Fibrosis in Aging.

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