Xie Jiayong, Chen Zhi, Yao Gang, Yuan Ying, Yu Wenjuan, Zhu Qiang
Department of Nephrology, Xinghua People's Hospital, Taizhou 225700, Jiangsu, China.
Kangda College of Nanjing Medical University, Lianyungang 222000, Jiangsu, China.
Regen Ther. 2022 Jun 17;21:87-95. doi: 10.1016/j.reth.2022.05.011. eCollection 2022 Dec.
Diabetic nephropathy (DN) is a severe diabetic complication and podocyte damage is a hallmark of DN. The Nucleoporin 160 (NUP160) gene was demonstrated to regulate cell proliferation and apoptosis in mouse podocytes. This study explored the possible role and mechanisms of NUP160 in high glucose-triggered podocyte injury. A rat model of DN was established by intraperitoneal injection of 60 mg/kg streptozotocin (STZ). Podocytes were treated with 33 mM high glucose. The effects of the Nup160 on DN and its mechanisms were assessed using MTT, flow cytometry, Western blot, ELISA, RT-qPCR, and luciferase reporter assays. The effects of NUP160 were analyzed by HE, PAS, and MASSON staining assays. The NUP160 level was significantly upregulated in podocytes treated with 33 mM high glucose. Functionally, NUP160 knockdown alleviated high glucose-induced apoptosis and inflammation in podocytes. Mechanistically, miR-495-3p directly targeted NUP160, and lncRNA HCG18 upregulated NUP160 by sponging miR-495-3p by acting as a ceRNA. Additionally, NUP160 overexpression reversed the effects of HCG18 knockdown in high glucose treated-podocytes. The assays indicated that NUP160 knockdown alleviated the symptoms of DN rats. NUP160 knockdown plays a key role in preventing the progression of DN, suggesting that targeting NUP160 may be a potential therapeutic strategy for DN treatment.
糖尿病肾病（DN）是一种严重的糖尿病并发症，足细胞损伤是DN的一个标志。已证明核孔蛋白160（NUP160）基因可调节小鼠足细胞的增殖和凋亡。本研究探讨了NUP160在高糖诱导的足细胞损伤中的可能作用及机制。通过腹腔注射60mg/kg链脲佐菌素（STZ）建立DN大鼠模型。足细胞用33mM高糖处理。使用MTT、流式细胞术、蛋白质免疫印迹法、酶联免疫吸附测定、逆转录-定量聚合酶链反应和荧光素酶报告基因测定评估Nup160对DN的影响及其机制。通过苏木精-伊红染色、过碘酸雪夫染色和马松三色染色分析NUP160的作用。在用33mM高糖处理的足细胞中，NUP160水平显著上调。在功能上，敲低NUP160可减轻高糖诱导的足细胞凋亡和炎症。机制上，miR-495-3p直接靶向NUP160，长链非编码RNA HCG18通过作为竞争性内源RNA（ceRNA）海绵吸附miR-495-3p来上调NUP160。此外，NUP160过表达逆转了敲低HCG18对高糖处理的足细胞的影响。实验表明，敲低NUP160可减轻DN大鼠的症状。敲低NUP160在预防DN进展中起关键作用，这表明靶向NUP160可能是DN治疗的一种潜在策略。
