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

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

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders

Volume 18 , Issue 3 , 2018

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Graphical 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.

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

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Article Details

Year: 2018
Published on: 30 January, 2018
Page: [241 - 250]
Pages: 10
DOI: 10.2174/1871530318666180131102707
Price: $65

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