IGF-1R Inhibitor Ameliorates Diabetic Nephropathy with Suppressed HMGN1/TLR4 Pathway

Title:IGF-1R Inhibitor Ameliorates Diabetic Nephropathy with Suppressed HMGN1/TLR4 Pathway

Volume: 18 Issue: 3

Author(s): Jiali Yu, Jingjing Da, Rong Dong, Yi Sun, Yingjie Nie, Fuxun Yu, Li Zuo and Yan Zha*

Affiliation:

• Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province,China

Keywords: IGF-1 receptor inhibitor, diabetic nephropathy, high-mobility group nucleosome-binding protein 1, Toll-like receptor 4, T1DM, diabetic.

Abstract: Objective: This study was established to investigate the contribution of high mobility group nucleosome-binding protein 1 (HMGN1)/ Toll-like receptor 4 (TLR4) pathway in diabetic nephropathy (DN). And as an intervention of the potential mechanism above, the insulin growth factor 1 receptor (IGF-1R) inhibitor was examined for its therapeutic effect in the diabetic mice.

Method: Male C57BL/6J mice were administered streptozotocin(STZ) to induce diabetes and thus divided into 5 groups: the untreated group (DN group), the benazepril-treated group (BEN-DN group), the insulin-treated group (INS-DN group) and the IGF-1R inhibitor-treated group (IGF-DN group). Immunohistochemistry and in situ hybrization were performed to detect the expression of HMGN1 and TLR4 in renal tissue. To evaluate the effect of IGF-1R inhibitor, levels of blood glucose and kidney/ body weight (KW/BW) were measured. And morphological changes and mesangial matrix expansion in kidneys were also detected.

Results: Increased expression of HMGN1 and TLR4 in renal tissue of STZ-induced type1 diabetic mellitus (T1DM) mice models was observed. IGF-1R inhibitor attenuate the established nephropathy with reduced expression of TLR4 protein, as revealed by a decrease in mesangial index.

Conclusion: IGF-1R inhibitor might have therapeutic potential in DN through inhibition of HMGN1/TLR4 pathway.

Cite this article as:

Yu Jiali , Da Jingjing , Dong Rong , Sun Yi , Nie Yingjie , Yu Fuxun , Zuo Li and Zha Yan *, IGF-1R Inhibitor Ameliorates Diabetic Nephropathy with Suppressed HMGN1/TLR4 Pathway, Endocrine, Metabolic & Immune Disorders - Drug Targets 2018; 18 (3) . https://dx.doi.org/10.2174/1871530318666180131102707