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KNOCKOUT OF SPHINGOSINE KINASE 1 ATTENUATES RENAL INTERSTITIAL FIBROSIS IN UNILATERAL URETERAL OBSTRUCTION (UUO) MODELZhang, Xiwen 01 January 2017 (has links)
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite and an important signaling molecule that plays a significant role in fibrosis. S1P synthesis is catalyzed by sphingosine kinases (SphKs), which phosphorylate sphingosine into S1P. The present study tested the hypothesis that SphK1-S1P signaling pathway participates in the kidney damage in unilateral ureteral obstruction (UUO) model. Wild type and SphK1 knockout mice were subjected to UUO for 7 days or 14 days and then four groups of kidneys were collected: wild type control group (WT-C), wild type UUO group (WT-UUO), SphK1-/- control group (KO-C) and SphK1-/- UUO group (KO-UUO). The mRNA level of SphK1 in WT-UUO was increased by 6.1 folds compared to WT-C. The fibrotic markers α-smooth muscle actin (α-SMA) and collagen I were both upregulated in UUO groups, whereas the levels of these two markers were significant lower in KO-UUO than that in WT-UUO. The immunohistochemistry analyses showed that the distribution of α-SMA and collagen was located in the interstitial space and that the infiltration of immune cells was more in UUO groups than that in control groups, but there was no significant difference between KO-UUO and WT-UUO, suggesting a direct effect of SphK1 deletion on renal fibrotic markers independent of immune regulation. Further, the morphological examination showed that UUO-induced tubular injury and glomerular damage were significantly reduced in KO-UUO compared with WT-UUO. Our study suggests that SphK1-S1P signaling pathway mediates kidney damage in UUO mice. Manipulating SphK1-S1P signaling pathway may be used as a therapeutic strategy in renal interstitial fibrosis.
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Einfluss von Transforming Growth Factor - beta 1 (TGF-β1) und Hypoxie auf die Expression von Sulfattransportern (SAT-1 und NaSi-1) in den humanen renalen Zelllinien TK173 und TK188 / Influence of Transforming Growth Factor beta 1 (TGF-β1) and hypoxia on the expression of sulfate-transporters (SAT-1 and NaSi-1) in the human renal cell lines TK173 and TK188von Fintel, Hendrik 10 October 2011 (has links)
No description available.
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