miR-30a-5p promotes glomerular podocyte apoptosis via DNMT1-mediated hypermethylation under hyperhom

• 作 者: Ning Ding Lin Xie Fei Ma Shengchao Ma Jiantuan Xiong Guanjun Lu Huiping Zhang Yideng Jiang
• 机 构: School of Basic Medical Sciences,Ningxia Medical University,Yinchuan 750004,China;NHC Key Laboratory
• 出 处: 生物化学与生物物理学报（英文版）
• 发表日期: 2022年1期
• 关键词: miR-30a-5p DNA methylation podocyte apoptosis FOXA1

Abnormal elevation of homocysteine(Hcy)level is closely related to the development and progression of chronic kidney disease(CKD),with the molecular mech2anisms that are not fully elucidated.Given the demonstration that miR-30a-5p is specifically expressed in glomerular podocytes,in the present study we aimed to investigate the role and potential underlying mechanism of miR-30a-5p in glomerular podocyte apoptosis induced by Hcy.We found that elevated Hcy downregulates miR-30a-5p expression in the Cbs+/-mice and Hcy-treated podocytes,and miR-30a-5p directly targets the 3\'-untranslated region(3\'-UTR)of the forkhead box A1(FOXA1)and overexpression of miR-30a-5p inhibits FOXA1 expression.By nMS-PCR and MassARRAY quantitative methylation analysis,we showed the increased DNA methylation level of miR-30a-5p promoter both in vivo and in vitro.Meanwhile,dual-luciferase reporter assay showed that the region between-1400 and-921 bp of miR-30a-5p promoter is a possible regulatory element for its transcription.Mechanistic studies indicated that DNA methyltransferase enzyme 1(DNMT1)is the key regulator of miR-30a-5p,which in turn enhances miR-30a-5p promoter methylation level and thereby inhibits its expression.Taken together,our results revealed that epigenetic modification of miR-30a-5p is involved in glomerular podocyte injury induced by Hcy,providing a diagnostic marker candidate and novel ther-apeutic target in CKD induced by Hcy.