Angiotensin II stimualtes fibronectin protein synthesis via a G βγ⁄arachidonic acid-dependent pathway.

In this study, we determined the effects of Ang II on fibronectin expression in cultured rabbit proximal tubule cells and elucidted the signaling pathways associated with such expression. We found that Ang II and transfection of Gβγ subunits directly increased fibronectin protein expression, and this increase was inhibited by overexpression of βARK-ct or a DN-Src. Moreover, Ang II-induced fibronectin protein expression was significantly abrogated by the AT2 receptor antagonist PD123319. In addition, inhibition of cPLA2) diminished Ang II-induced fibronectin expression. Endogenous arachidonic acid mimicked Ang II-induced fibronectin expression. We also found that overexpression of Gβγ subunits induced c-Src, ERK1/2 and EGFR tyrosine phosphorylation, which can be inhibited by overexpression of βARK-ct or DN-Src. Gβγ also induced c-Src SH2 domain association with the EGFR. Supporting these findings, in rabbit proximal tubular epithelium, immunoblot analysis indicated that βγ expression was significant. Interestingly, arachidonic acid- and ETYA-induced responses were preserved in the presence of βARK-ct. This is the first report demonstrating the regulation of EGFR, ERK1/2, c-Src, and fibronectin by Gβγ subunits in renal epithelial cells. Moreover, this work demonstrates a role for Gβγ heterotrimeric proteins in Ang II, but not arachidonic acid signaling, in renal epithelial cells. PMID: 24920755 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research