PIK-III exerts anti-fibrotic effects in activated fibroblasts by regulating p38 activation.

ABSTRACT: Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune-driven connective tissue disorder that results in fibrosis of the skin and internal organs such as the lung. Fibroblasts are known as the main effector cells involved in the progression of SSc through the induction of extracellular matrix (ECM) proteins and myofibroblast differentiation. Here, we demonstrate that 4'-(cyclopropylmethyl)-N2-4-pyridinyl-[4,5'-bipyrimidine]-2,2'-diamine (PIK-III), known as class III phosphatidylinositol 3-kinase (PIK3C3/VPS34) inhibitor, exerts potent antifibrotic effects in human dermal fibroblasts (HDFs) by attenuating transforming growth factor-beta 1 (TGF-β1)-induced ECM expression, cell contraction and myofibroblast differentiation. Unexpectedly, neither genetic silencing of PIK3C3 nor

SUBMITTER: Sanchez S 

PROVIDER: S-EPMC11379285 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature