PAI-1 mediates TGF-β1-induced myofibroblast activation in tenocytes via mTOR signaling.

ABSTRACT: Transforming growth factor-beta (TGF-β1) induces plasminogen activator inhibitor 1 (PAI-1) to effect fibrotic pathologies in several organs including tendon. Recent data implicated PAI-1 with inhibition of phosphatase and tensin homolog (PTEN) suggesting that PAI-1-induced adhesions involves phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) signaling. Ergo, we investigated effects of TGF-β1, PAI-1, and mTOR signaling crosstalk on myofibroblast activation, senescence, and proliferation in primary flexor tenocytes from wild-type (WT) and PAI-1 knockout (KO) mice. PAI-1 deletion blunted TGF-β1-induced myofibroblast activation in murine flexor tenocytes and increased the gene expression of Mmp-2 to confer protective effects against fibrosis. While TGF-β1 significa

SUBMITTER: Alenchery RG 

PROVIDER: S-EPMC10524825 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature