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Endocrine, metabolic & immune disorders drug targets · 2018

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

СтатьяНазвание и аннотация: Перевод в очереди
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Yu Jiali, Da Jingjing, Dong Rong, Sun Yi, Nie Yingjie, Yu Fuxun, Zuo Li, Zha Yan

Аннотация

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.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты