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