Fructose downregulates miR-330 to induce renal inflammatory response and insulin signaling impairment: Attenuation by morin
Fructose downregulates miR-330 to induce renal inflammatory response and insulin signaling impairment: Attenuation by morin
复制标题
果糖下调 miR-330 诱导肾脏炎症反应和胰岛素信号传导损伤：桑色素的减弱作用
DOI：
10.1002/mnfr.201600760
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发表时间：
2017-08-01
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：
Gu, Ting-Ting;Song, Lin;Kong, Ling-Dong
范围：果糖会诱导胰岛素抵抗，导致肾脏炎症和损伤。 MicroRNA 已成为胰岛素信号传导的关键调节因子。桑色素具有类胰岛素作用，可改善胰岛素抵抗和肾损伤。本研究探讨了桑色素对果糖诱导的肾损伤的保护机制，特别关注miR-330表达变化、炎症反应和胰岛素信号损伤。方法和结果：miR-330、鞘氨醇激酶1（SphK1）/鞘氨醇-1-磷酸（S1P）/S1受体（S1PR）1/3信号、核因子-κB（NF-κ） B) 在果糖喂养的大鼠和暴露于果糖的 HK-2 细胞的肾皮质中分别检测到 B)/NOD 样受体家族、含热蛋白结构域 3 (NLRP3) 炎性体和胰岛素信号传导。分别使用 SphK1 抑制剂、S1PR1/3 短干扰 RNA 或 miR-330 模拟物/抑制剂检查 miR-330 是否介导炎症反应以影响胰岛素信号传导。研究发现果糖可下调 miR-330 表达，增加 SphK1/S1P/S1PR1/3 信号传导，然后激活 NF-kappa B/NLRP3 炎性体产生 IL-1 beta，导致胰岛素信号传导受损。此外，桑色素上调miR-330并部分减弱炎症反应和胰岛素信号损伤，从而减轻肾损伤。结论：这些研究结果表明桑色素通过上调miR-330减少炎症反应来防止果糖诱导的肾胰岛素信号损伤。桑色素可能是治疗与果糖诱导的炎症和胰岛素信号传导损伤相关的肾损伤的潜在治疗剂。
Scope: Fructose induces insulin resistance with kidney inflammation and injury. MicroRNAs are emerged as key regulators of insulin signaling. Morin has insulin-mimetic effect with the improvement of insulin resistance and kidney injury. This study investigated the protective mechanisms of morin against fructose-induced kidney injury, with particular focus onmiR-330 expression change, inflammatory response, and insulin signaling impairment.Methods and results: miR-330, sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)/S1preceptor (S1PR) 1/3 signaling, nuclear factor-kappa B (NF-kappa B)/NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, and insulin signaling were detected in kidney cortex of fructose-fed rats and fructose-exposed HK-2 cells, respectively. Whether miR-330 mediated inflammatory response to affect insulin signaling was examined using SphK1 inhibitor, S1PR1/3 short interfering RNA, or miR-330 mimic/inhibitor, respectively. Fructose was found to downregulate miR-330 expression to increase SphK1/S1P/S1PR1/3 signaling, and then activate NF-kappa B/NLRP3 inflammasome to produce IL-1 beta, causing insulin signaling impairment. Moreover, morin upregulated miR-330 and partly attenuated inflammatory response and insulin signaling impairment to alleviate kidney injury.Conclusion: These findings suggest thatmorin protects against fructose-induced kidney insulin signaling impairment by upregulating miR-330 to reduce inflammatory response. Morin may be a potential therapeutic agent for the treatment of kidney injury associated with fructose-induced inflammation and insulin signaling impairment.