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Kidney Blood Press Res. 2013;38(1):156-64. doi: 10.1159/000355763. Epub 2014 Mar 15.

PKB/SGK-resistant GSK-3 signaling following unilateral ureteral obstruction.

Author information

1
Department of Physiology, University of Tübingen, Tübingen, Germany.

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-3(KI)) and corresponding wild-type mice (gsk-3(WT)). 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-3(KI) mice but was increased by UUO in kidney tissues from gsk-3(WT) 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-3(KI) mice and gsk-3(WT) mice but was significantly less increased in the obstructed kidney tissues from gsk-3(KI) mice than from gsk-3(WT) 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-3(KI) mice than from gsk-3(WT) 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.

PMID:
24685987
DOI:
10.1159/000355763
[Indexed for MEDLINE]
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