TGFβ receptor I transactivation mediates stretch-induced Pak1 activation and CTGF upregulation in mesangial cells.

ABSTRACT: Increased intraglomerular pressure is an important pathogenic determinant of kidney fibrosis in the progression of chronic kidney disease, and can be modeled by exposing glomerular mesangial cells (MC) to mechanical stretch. MC produce extracellular matrix and profibrotic cytokines, including connective tissue growth factor (CTGF) when stretched. We show that p21-activated kinase 1 (Pak1) is activated by stretch in MC in culture and in vivo in a process marked by elevated intraglomerular pressures. Its activation is essential for CTGF upregulation. Rac1 is an upstream regulator of Pak1 activation. Stretch induces transactivation of the type I transforming growth factor β1 receptor (TβRI) independently of ligand binding. TβRI transactivation is required not only for Rac1/Pak1 activation, bu

SUBMITTER: Chen G 

PROVIDER: S-EPMC3744028 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature