Targeting Mechanics-Induced Fibroblast Activation through CD44-RhoA-YAP Pathway Ameliorates Crystalline Silica-Induced Silicosis.

ABSTRACT: Silicosis is pneumoconiosis of the lung, usually resulting from prolonged exposure to crystalline silica (CS). The hallmark of silicosis is excessive extracellular matrix (ECM) deposition produced by activated fibroblasts. Recent work demonstrated that excessive ECM-forming mechanical cues play an essential role in promoting fibroblast activation and perpetuating fibrotic pathologies. However, the detailed molecular mechanism still needs to be uncovered. Methods: NIH-3T3 fibroblasts were cultured on either 1 kappa (soft) or 60 kappa (stiff) gel-coated coverslips. A series of knockdown and reverse experiments in vitro were performed to establish the signaling for mechanics-induced fibroblast activation. An experimental model of silicosis was established by one-time intratrache

SUBMITTER: Li S 

PROVIDER: S-EPMC6691376 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature