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.

Ning Ding;Lin Xie;Fei Ma;Shengchao Ma;Jiantuan Xiong;Guanjun Lu;Huiping Zhang;Yideng Jiang

School of Basic Medical Sciences,Ningxia Medical University,Yinchuan 750004,China;NHC Key Laboratory of Metabolic Cardiovascular Diseases Research,Ningxia Medical University,Yinchuan 750004,China;Ningxia Key Laboratory of Vascular Injury and Repair Research,Ningxia Medical University,Yinchuan 750004,China;Department of Clinical Medicine,General Hospital of Ningxia Medical University,Yinchuan 750004,China;Prenatal Diagnosis Center,General Hospital of Ningxia Medical University,Yinchuan 750004,China

生物化学与生物物理学报（英文版）

[1]Ning Ding;Lin Xie;Fei Ma;Shengchao Ma;Jiantuan Xiong;Guanjun Lu;Huiping Zhang;Yideng Jiang-.miR-30a-5p promotes glomerular podocyte apoptosis via DNMT1-mediated hypermethylation under hyperhomocysteinemia)[J].生物化学与生物物理学报（英文版）,2022(01):126-136

mech2anisms,Cbs+

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