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

[ Vol. 18 , Issue. 3 ]

Author(s):

Jiali Yu, Jingjing Da, Rong Dong, Yi Sun, Yingjie Nie, Fuxun Yu, Li Zuo and Yan Zha*   Pages 241 - 250 ( 10 )

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.

Affiliation:

Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, Department of Immunology, Guizhou Medical University, Guiyang, Guizhou Province, Department of Science and Technology, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, Central lab, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province, Department of Immunology, Guizhou Medical University, Guiyang, Guizhou Province, Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang, Guizhou Province

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