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The effects of an endothelial N-deacetylase-N-sulfotransferase knock out on diabetic renal disease

Kel B., (2015) The effects of an endothelial N-deacetylase-N-sulfotransferase knock out on diabetic renal disease. Master's Thesis / Essay, Biology.

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Abstract

Inflammatory responses are involved in the progression of diabetic nephropathy. Recent studies suggest that heparan sulfate, the major component of the endothelia glycocalyx, is associated with endothelial function in inflammation. However, the contribution of heparan sulfate to DN and the precise mechanisms are unclear. Therefore the aim of this study is to investigate the effects of a vascular endothelial Nndst1 knock out in diabetic mice. Age matched C57B1/6J- WT and Cre+ NDST f/f mice were intraperitoneally injected with Streptozotocin (50mg/kg) to indcue diabetes or citrate buffer as a control for five days. After two weeks and two months follow up urine and plasma were collected, where after kidneys are immunohistochemically stained for macrophages, neutrophils, C3b, MBL and collagen type III. The ELISA method is used to measure albuminuria and qPCR is performed to measure mRNA-expression of specific markers. Primers used for qPCR are housekeeping gene 36B4, Lipocalin-2 (NGAL), Vimentin, TGF-B1 and collagen type I. In Ndst1 deficient mice, the development of DN was associated with a reduced macrophage influx and size of macrophages. In contrast, no significant differences are found in neutrophil influx, C3b deposition and MBL expression among the groups. Furthermore, a Ndst1 deficiency showed decreased interstitial fibrosis evidences by lower expression of Vimentin, TGF-B1 and collagen type I. Diabetes of 90 days resulted in albuminuria and Ndst1 deficient mice showed a trend toward more albuminuria, however not significant. In conclusion, our results revealed that Ndst1 deficient diabetic mice show less accumulation of macrophages, which might cause the reduction in renal fibrosis. we showed a clear association between inflammatory molecules and heparan sulfate, which indicates the importance of heparan sulfate in diabetic kidney diseases. However, future research is needed to increase our understanding of the precise mechanisms and regulation of heparan sulfate interactions in different inflammatory and fibrotic responses.

Item Type: Thesis (Master's Thesis / Essay)
Degree programme: Biology
Thesis type: Master's Thesis / Essay
Language: English
Date Deposited: 15 Feb 2018 08:08
Last Modified: 15 Feb 2018 08:08
URI: http://fse.studenttheses.ub.rug.nl/id/eprint/13365

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