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http://purl.uniprot.org/citations/24685987http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24685987http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/24685987http://purl.org/dc/terms/identifier"doi:10.1159/000355763"xsd:string
http://purl.uniprot.org/citations/24685987http://purl.uniprot.org/core/author"Alessi D.R."xsd:string
http://purl.uniprot.org/citations/24685987http://purl.uniprot.org/core/author"Walker B."xsd:string
http://purl.uniprot.org/citations/24685987http://purl.uniprot.org/core/author"Lang F."xsd:string
http://purl.uniprot.org/citations/24685987http://purl.uniprot.org/core/author"Ahmed M.S."xsd:string
http://purl.uniprot.org/citations/24685987http://purl.uniprot.org/core/author"Meissner A."xsd:string
http://purl.uniprot.org/citations/24685987http://purl.uniprot.org/core/author"Elvira B."xsd:string
http://purl.uniprot.org/citations/24685987http://purl.uniprot.org/core/author"Alesutan I."xsd:string
http://purl.uniprot.org/citations/24685987http://purl.uniprot.org/core/author"Mia S."xsd:string
http://purl.uniprot.org/citations/24685987http://purl.uniprot.org/core/author"Voelkl J."xsd:string
http://purl.uniprot.org/citations/24685987http://purl.uniprot.org/core/author"Feger M."xsd:string
http://purl.uniprot.org/citations/24685987http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/24685987http://purl.uniprot.org/core/name"Kidney Blood Press Res"xsd:string
http://purl.uniprot.org/citations/24685987http://purl.uniprot.org/core/pages"156-164"xsd:string
http://purl.uniprot.org/citations/24685987http://purl.uniprot.org/core/title"PKB/SGK-resistant GSK-3 signaling following unilateral ureteral obstruction."xsd:string
http://purl.uniprot.org/citations/24685987http://purl.uniprot.org/core/volume"38"xsd:string
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