GPCR-induced YAP activation sensitizes fibroblasts to profibrotic activity of TGFβ1.

ABSTRACT: Tissue fibrosis is a pathological condition characterized by uncontrolled fibroblast activation that ultimately leads to organ failure. The TGFβ1 pathway, one of the major players in establishment of the disease phenotype, is dependent on the transcriptional co-activators YAP/TAZ. We were interested whether fibroblasts can be sensitized to TGFβ1 by activation of the GPCR/YAP/TAZ axis and whether this mechanism explains the profibrotic properties of diverse GPCR ligands. We found that LPA, S1P and thrombin cooperate in human dermal fibroblasts with TGFβ1 to induce extracellular matrix synthesis, myofibroblast marker expression and cytokine secretion. Whole genome expression profiling identified a YAP/TAZ signature behind the synergistic profibrotic effects of LPA and TGFβ1. LPA, S1P and thr

SUBMITTER: Zmajkovicova K 

PROVIDER: S-EPMC7018035 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature