Cargando…

miR-30a-5p promotes glomerular podocyte apoptosis via DNMT1-mediated hypermethylation under hyperhomocysteinemia: miR-30a-5p in podocyte apoptosis

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 presen...

Descripción completa

Detalles Bibliográficos
Autores principales: Ding, Ning, Xie, Lin, Ma, Fei, Ma, Shengchao, Xiong, Jiantuan, Lu, Guanjun, Zhang, Huiping, Jiang, Yideng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909319/
https://www.ncbi.nlm.nih.gov/pubmed/35130620
http://dx.doi.org/10.3724/abbs.2021005
_version_ 1784884548080762880
author Ding, Ning
Xie, Lin
Ma, Fei
Ma, Shengchao
Xiong, Jiantuan
Lu, Guanjun
Zhang, Huiping
Jiang, Yideng
author_facet Ding, Ning
Xie, Lin
Ma, Fei
Ma, Shengchao
Xiong, Jiantuan
Lu, Guanjun
Zhang, Huiping
Jiang, Yideng
author_sort Ding, Ning
collection PubMed
description 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 therapeutic target in CKD induced by Hcy.
format Online
Article
Text
id pubmed-9909319
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-99093192023-02-10 miR-30a-5p promotes glomerular podocyte apoptosis via DNMT1-mediated hypermethylation under hyperhomocysteinemia: miR-30a-5p in podocyte apoptosis Ding, Ning Xie, Lin Ma, Fei Ma, Shengchao Xiong, Jiantuan Lu, Guanjun Zhang, Huiping Jiang, Yideng Acta Biochim Biophys Sin (Shanghai) Research Article 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 therapeutic target in CKD induced by Hcy. Oxford University Press 2021-12-28 /pmc/articles/PMC9909319/ /pubmed/35130620 http://dx.doi.org/10.3724/abbs.2021005 Text en © The Author(s) 2021. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/).
spellingShingle Research Article
Ding, Ning
Xie, Lin
Ma, Fei
Ma, Shengchao
Xiong, Jiantuan
Lu, Guanjun
Zhang, Huiping
Jiang, Yideng
miR-30a-5p promotes glomerular podocyte apoptosis via DNMT1-mediated hypermethylation under hyperhomocysteinemia: miR-30a-5p in podocyte apoptosis
title miR-30a-5p promotes glomerular podocyte apoptosis via DNMT1-mediated hypermethylation under hyperhomocysteinemia: miR-30a-5p in podocyte apoptosis
title_full miR-30a-5p promotes glomerular podocyte apoptosis via DNMT1-mediated hypermethylation under hyperhomocysteinemia: miR-30a-5p in podocyte apoptosis
title_fullStr miR-30a-5p promotes glomerular podocyte apoptosis via DNMT1-mediated hypermethylation under hyperhomocysteinemia: miR-30a-5p in podocyte apoptosis
title_full_unstemmed miR-30a-5p promotes glomerular podocyte apoptosis via DNMT1-mediated hypermethylation under hyperhomocysteinemia: miR-30a-5p in podocyte apoptosis
title_short miR-30a-5p promotes glomerular podocyte apoptosis via DNMT1-mediated hypermethylation under hyperhomocysteinemia: miR-30a-5p in podocyte apoptosis
title_sort mir-30a-5p promotes glomerular podocyte apoptosis via dnmt1-mediated hypermethylation under hyperhomocysteinemia: mir-30a-5p in podocyte apoptosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909319/
https://www.ncbi.nlm.nih.gov/pubmed/35130620
http://dx.doi.org/10.3724/abbs.2021005
work_keys_str_mv AT dingning mir30a5ppromotesglomerularpodocyteapoptosisviadnmt1mediatedhypermethylationunderhyperhomocysteinemiamir30a5pinpodocyteapoptosis
AT xielin mir30a5ppromotesglomerularpodocyteapoptosisviadnmt1mediatedhypermethylationunderhyperhomocysteinemiamir30a5pinpodocyteapoptosis
AT mafei mir30a5ppromotesglomerularpodocyteapoptosisviadnmt1mediatedhypermethylationunderhyperhomocysteinemiamir30a5pinpodocyteapoptosis
AT mashengchao mir30a5ppromotesglomerularpodocyteapoptosisviadnmt1mediatedhypermethylationunderhyperhomocysteinemiamir30a5pinpodocyteapoptosis
AT xiongjiantuan mir30a5ppromotesglomerularpodocyteapoptosisviadnmt1mediatedhypermethylationunderhyperhomocysteinemiamir30a5pinpodocyteapoptosis
AT luguanjun mir30a5ppromotesglomerularpodocyteapoptosisviadnmt1mediatedhypermethylationunderhyperhomocysteinemiamir30a5pinpodocyteapoptosis
AT zhanghuiping mir30a5ppromotesglomerularpodocyteapoptosisviadnmt1mediatedhypermethylationunderhyperhomocysteinemiamir30a5pinpodocyteapoptosis
AT jiangyideng mir30a5ppromotesglomerularpodocyteapoptosisviadnmt1mediatedhypermethylationunderhyperhomocysteinemiamir30a5pinpodocyteapoptosis