Lin Yuan, Yin Chaoyan, Liu Yanjing, Lu Donghui, Lian Xiaofen
Department of Endocrinology, Peking University, Shenzhen, Guangdong, China
Department of Nuclear Medicine Shenzhen Hospital, Peking University, Shenzhen, Guangdong, China.
Ann Clin Lab Sci. 2025 Jan;55(1):48-53.
Chronic diabetic nephropathy (CDN) is one of the common complications of the chronic diabetes. The FGF23/FGFR3-mediated signaling pathway is involved in CDN. Whether miR-190a-3P participates in CDN through regulation of FGFR3 remains to be elucidated. The present study evaluated miR-190a-3P's effect on CDN.
Mice were divided into a control group (NC group), a CDN group, and CDN+miR-190a-3P antagonist group, followed by analysis of miR-190a-3P and FGFR3 level by qRT-PCR, FGFR3, and Tubulin protein level by Western blot as well as blood glucose, serum creatinine (Cr), and urea nitrogen (BUN) using an automatic biochemical analyzer.
Compared with the NC group, the CDN group had a significantly higher miR-190a-3P level in kidney tissue, while the FGFR3 mRNA level was lower (<0.01). FGFR3 was a target gene of miR-190a-3P. miR-190a-3P levels in the CDN+miR-190a-3P antagonist group were significantly reduced compared with the CDN group (<0.05). Meanwhile, FGFR3 protein levels in miR-190a-3P antagonist group were significantly increased (<0.05). Compared with the NC group, the CDN group showed significantly reduced blood glucose level and elevated BUN and Cr level (<0.01). However, CDN+miR-190a-3P antagonist group showed significantly increased blood glucose and reduced BUN and Cr level compared with CDN group (<0.05).
miR-190a-3P can directly bind to the 3'-UTR of FGFR3 mRNA and reduce FGFR3 protein levels, contributing to the occurrence of CDN.
慢性糖尿病肾病（CDN）是慢性糖尿病常见并发症之一。成纤维细胞生长因子23（FGF23）/成纤维细胞生长因子受体3（FGFR3）介导的信号通路参与慢性糖尿病肾病的发生发展。微小RNA-190a-3p（miR-190a-3P）是否通过调控FGFR3参与慢性糖尿病肾病的发生发展尚待阐明。本研究旨在评估miR-190a-3P对慢性糖尿病肾病的影响。
将小鼠分为对照组（NC组）、慢性糖尿病肾病组（CDN组）和慢性糖尿病肾病+miR-190a-3P拮抗剂组，采用实时定量逆转录聚合酶链反应（qRT-PCR）检测miR-190a-3P和FGFR3水平，蛋白质免疫印迹法检测FGFR3和微管蛋白（Tubulin）蛋白水平，自动生化分析仪检测血糖、血清肌酐（Cr）和尿素氮（BUN）水平。
与NC组相比，CDN组肾组织中miR-190a-3P水平显著升高，而FGFR3信使核糖核酸（mRNA）水平降低（<0.01）。FGFR3是miR-190a-3P的靶基因。与CDN组相比，慢性糖尿病肾病+miR-190a-3P拮抗剂组中miR-190a-3P水平显著降低（<0.05）。同时，miR-190a-3P拮抗剂组中FGFR3蛋白水平显著升高（<0.05）。与NC组相比，CDN组血糖水平显著降低，BUN和Cr水平升高（<0.01）。然而，与CDN组相比，慢性糖尿病肾病+miR-190a-3P拮抗剂组血糖显著升高，BUN和Cr水平降低（<0.05）。
miR-190a-3P可直接结合FGFR3 mRNA的3'-非翻译区（3'-UTR），降低FGFR3蛋白水平，促进慢性糖尿病肾病的发生。
