We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
PKB/SGK-Resistant GSK-3 Signaling Following Unilateral Ureteral Obstruction.
- Authors
Voelkl, Jakob; Mia, Sobuj; Meissner, adrian; ahmed, Mohamed S.; Feger, Martina; Elvira, Bernat; Walker, Britta; alessi, Dario R.; alesutan, Ioana; Lang, Florian
- Abstract
Background/Aims: Renal tissue fibrosis contributes to the development of end-stage renal disease. Causes for renal tissue fibrosis include obstructive nephropathy. The development of renal fibrosis following unilateral ureteral obstruction (UUO) is blunted in gene-targeted mice lacking functional serum- and glucocorticoid-inducible kinase SGK1. Similar to Akt isoforms, SGK1 phosphorylates and thus inactivates glycogen synthase kinase GSK-3. The present study explored whether PKB/SGK-dependent phoshorylation of GSK-3α/β impacts on pro-fibrotic signaling following UUO. Methods: UUO was induced in mice carrying a PKB/SGK-resistant GSK-3α/β (gsk-3KI) and corresponding wild-type mice (gsk-3WT). Three days after the obstructive injury, expression of fibrosis markers in kidney tissues was analyzed by quantitative RT-PCR and western blotting. Results: GSK-3α and GSK-3β phosphorylation was absent in both, the non-obstructed and the obstructed kidney tissues from gsk-3KI mice but was increased by UUO in kidney tissues from gsk-3WT mice. Expression of α-smooth muscle actin, type I collagen and type III collagen in the non-obstructed kidney tissues was not significantly different between gsk-3KI mice and gsk-3WT mice but was significantly less increased in the obstructed kidney tissues from gsk-3KI mice than from gsk-3WT mice. After UUO treatment, renal β-catenin protein abundance and renal expression of the β-catenin sensitive genes: c-Myc, Dkk1, Twist and Lef1 were again significantly less increased in kidney tissues from gsk-3KI mice than from gsk-3WT mice. Conclusions: PKB/SGK-dependent phosphorylation of glycogen synthase kinase GSK-3 contributes to the pro-fibrotic signaling leading to renal tissue fibrosis in obstructive nephropathy. © 2014 S. Karger AG, Basel
- Subjects
KIDNEY diseases; RENAL fibrosis; URETERIC obstruction; KINASE genetics; GLUCOCORTICOIDS; SGK protein; PHOSPHORYLATION
- Publication
Kidney & Blood Pressure Research, 2014, Vol 38, Issue 1, p156
- ISSN
1420-4096
- Publication type
Article
- DOI
10.1159/000355763