Curcumin protects against fructose-induced podocyte insulin signaling impairment through upregulation of miR-206
Curcumin protects against fructose-induced podocyte insulin signaling impairment through upregulation of miR-206
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DOI：
10.1002/mnfr.201500370
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发表时间：
2015-12-01
影响因子：
5.2
通讯作者：
Kong, Ling-Dong
中科院分区：
文献类型：
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作者：
Ding, Xiao-Qin;Gu, Ting-Ting;Kong, Ling-Dong
范围：摄入果糖可导致胰岛素抵抗和代谢综合征，与肾小球足细胞功能障碍和蛋白尿有关。本研究探讨果糖在足细胞功能障碍和损伤中是否引起胰岛素信号转导障碍，以及姜黄素是否能减轻这种损伤。方法和结果：大鼠喂饲10%果糖6周，然后口服姜黄素6周。评估代谢综合征、足细胞损伤、microRNA表达和胰岛素信号转导。姜黄素可显著减轻果糖所致大鼠肾皮质或肾小球中果糖诱导的足细胞损伤和蛋白尿、miR-206低表达、蛋白酪氨酸磷酸酶1B(PTP1B)的高表达，下调胰岛素受体、胰岛素受体底物1、小窝蛋白1、蛋白激酶B以及细胞外信号调节激酶1和2的磷酸化水平。这些作用在5 mM果糖诱导的分化足细胞中得到了进一步证实，包括姜黄素、PTP1B siRNA、慢病毒介导的PTP1B重组过表达、miR-206模拟或miR-206抑制剂转染，提示miR-206上调可能通过调节PTP1B的表达而促进胰岛素信号转导。结论：姜黄素可能通过激活miR-206表达下调PTP1B，进而改善胰岛素信号转导，保护肾小球细胞免受果糖所致的肾小球足细胞损伤，从而为研究姜黄素对果糖相关足细胞损伤的作用提供新的证据。
Scope: Fructose consumption can induce insulin resistance and metabolic syndrome, which are associated with glomerular podocyte dysfunction and proteinuria. This study investigated whether fructose caused insulin signaling impairment in podocyte dysfunction and injury, and whether curcumin reduced these disturbances.Methods and results: Rats were fed with 10% fructose for 6 weeks and then orally cotreated with curcumin for next 6 weeks. Metabolic syndrome, podocyte injury, microRNA expression, and insulin signaling were evaluated. Curcumin significantly alleviated fructose-induced podocyte injury and proteinuria, miR-206 low-expression, protein tyrosine phosphatase 1B (PTP1B) overexpression, as well as downregulation of insulin receptor, insulin receptor substrate 1, caveolin-1, protein kinase B, and extracellular signal-regulated kinases 1 and 2 phosphorylation in kidney cortex or glomeruli of fructose-fed rats. These effects were further confirmed in cultured differentiated podocytes exposed to 5 mM fructose in the presence or absence of curcumin, PTP1B siRNA, lentivirus-mediated PTP1B recombinant overexpression, miR-206 mimic, or miR-206 inhibitor transfection, showing that miR-206 upregulation may contribute to improve insulin signaling through regulating PTP1B expression.Conclusion: Curcumin is suggested to activate miR-206 expression to downregulate PTP1B, and then improve insulin signaling, protect against fructose-induced glomerular podocyte injury, and proteinuria, which may provide new evidence regarding curcumin's effects on fructose-associated podocyte injury.