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• W2037773035 abstract "<b><i>Background/Aims: </i></b>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. <b><i>Methods: </i></b>UUO was induced in mice carrying a PKB/SGK-resistant GSK-3α/β (<i>gsk-3</i>^<i>KI</i>) and corresponding wild-type mice (<i>gsk-3</i>^<i>WT</i>). Three days after the obstructive injury, expression of fibrosis markers in kidney tissues was analyzed by quantitative RT-PCR and western blotting. <b><i>Results: </i></b>GSK-3α and GSK-3β phosphorylation was absent in both, the non-obstructed and the obstructed kidney tissues from <i>gsk-3</i>^<i>KI</i> mice but was increased by UUO in kidney tissues from <i>gsk-3</i>^<i>WT</i> 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 <i>gsk-3</i>^<i>KI</i> mice and <i>gsk-3</i>^<i>WT</i> mice but was significantly less increased in the obstructed kidney tissues from <i>gsk-3</i>^<i>KI</i> mice than from <i>gsk-3</i>^<i>WT</i> mice. After UUO treatment, renal β-catenin protein abundance and renal expression of the β-catenin sensitive genes: <i>c-Myc</i>, <i>Dkk1</i>,<i> Twist</i> and <i>Lef1</i> were again significantly less increased in kidney tissues from <i>gsk-3</i>^<i>KI</i> mice than from <i>gsk-3</i>^<i>WT</i> mice. <b><i>Conclusions: </i></b>PKB/SGK-dependent phosphorylation of glycogen synthase kinase GSK-3 contributes to the pro-fibrotic signaling leading to renal tissue fibrosis in obstructive nephropathy." @default.
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• W2037773035 date "2013-01-01" @default.
• W2037773035 modified "2023-09-25" @default.
• W2037773035 title "PKB/SGK-Resistant GSK-3 Signaling Following Unilateral Ureteral Obstruction" @default.
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• W2037773035 doi "https://doi.org/10.1159/000355763" @default.
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