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Sp1-Induced lncRNA Rmrp Promotes Mesangial Cell Proliferation and Fibrosis in Diabetic Nephropathy by Modulating the miR-1a-3p/JunD Pathway

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. Long non-coding RNAs (lncRNAs) are regulators in DN progression. However, the regulatory mechanisms of multiple lncRNAs in DN remain to be determined. Our aim was to investigate the function and molecular mechanism of lncRNA R...

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Autores principales: Yang, Hansen, Wang, Jia, Zhang, Zheng, Peng, Rui, Lv, Dan, Liu, Handeng, Sun, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429906/
https://www.ncbi.nlm.nih.gov/pubmed/34512545
http://dx.doi.org/10.3389/fendo.2021.690784
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author Yang, Hansen
Wang, Jia
Zhang, Zheng
Peng, Rui
Lv, Dan
Liu, Handeng
Sun, Yan
author_facet Yang, Hansen
Wang, Jia
Zhang, Zheng
Peng, Rui
Lv, Dan
Liu, Handeng
Sun, Yan
author_sort Yang, Hansen
collection PubMed
description Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. Long non-coding RNAs (lncRNAs) are regulators in DN progression. However, the regulatory mechanisms of multiple lncRNAs in DN remain to be determined. Our aim was to investigate the function and molecular mechanism of lncRNA RNA component of mitochondrial RNAase P (Rmrp) in DN. Here, we observed that the expression of Rmrp was up-regulated in the kidney of db/db DN mice and high glucose induced glomerular mesangial cells (MC). More importantly, the abnormal transcription of Rmrp was induced by nuclear transcription factor Sp1, which promotes the proliferation and production of fibrotic markers in MC. Subsequently, we screened the miRNAs related to Rmrp and found that Rmrp and miR-1a-3p are co-localized at the subcellular level of MC, and Rmrp could directly binds to miR-1a-3p. Further mechanism research demonstrated that the elevated miR-1a-3p significantly attenuated the proliferation and fibrosis-promoting effects induced by up-regulation of Rmrp. At the same time, we also investigated that miR-1a-3p can directly bind to Jun D proto-oncogene (JunD), thereby regulating the protein level of JunD. Rmrp-induced proliferation and fibrogenesis were reversed by co-transfection with JunD siRNA. In summary, Sp1 induced lncRNA Rmrp could drive the expression of JunD via sponging miR-1a-3p in DN progression.
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spelling pubmed-84299062021-09-11 Sp1-Induced lncRNA Rmrp Promotes Mesangial Cell Proliferation and Fibrosis in Diabetic Nephropathy by Modulating the miR-1a-3p/JunD Pathway Yang, Hansen Wang, Jia Zhang, Zheng Peng, Rui Lv, Dan Liu, Handeng Sun, Yan Front Endocrinol (Lausanne) Endocrinology Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. Long non-coding RNAs (lncRNAs) are regulators in DN progression. However, the regulatory mechanisms of multiple lncRNAs in DN remain to be determined. Our aim was to investigate the function and molecular mechanism of lncRNA RNA component of mitochondrial RNAase P (Rmrp) in DN. Here, we observed that the expression of Rmrp was up-regulated in the kidney of db/db DN mice and high glucose induced glomerular mesangial cells (MC). More importantly, the abnormal transcription of Rmrp was induced by nuclear transcription factor Sp1, which promotes the proliferation and production of fibrotic markers in MC. Subsequently, we screened the miRNAs related to Rmrp and found that Rmrp and miR-1a-3p are co-localized at the subcellular level of MC, and Rmrp could directly binds to miR-1a-3p. Further mechanism research demonstrated that the elevated miR-1a-3p significantly attenuated the proliferation and fibrosis-promoting effects induced by up-regulation of Rmrp. At the same time, we also investigated that miR-1a-3p can directly bind to Jun D proto-oncogene (JunD), thereby regulating the protein level of JunD. Rmrp-induced proliferation and fibrogenesis were reversed by co-transfection with JunD siRNA. In summary, Sp1 induced lncRNA Rmrp could drive the expression of JunD via sponging miR-1a-3p in DN progression. Frontiers Media S.A. 2021-08-27 /pmc/articles/PMC8429906/ /pubmed/34512545 http://dx.doi.org/10.3389/fendo.2021.690784 Text en Copyright © 2021 Yang, Wang, Zhang, Peng, Lv, Liu and Sun https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Yang, Hansen
Wang, Jia
Zhang, Zheng
Peng, Rui
Lv, Dan
Liu, Handeng
Sun, Yan
Sp1-Induced lncRNA Rmrp Promotes Mesangial Cell Proliferation and Fibrosis in Diabetic Nephropathy by Modulating the miR-1a-3p/JunD Pathway
title Sp1-Induced lncRNA Rmrp Promotes Mesangial Cell Proliferation and Fibrosis in Diabetic Nephropathy by Modulating the miR-1a-3p/JunD Pathway
title_full Sp1-Induced lncRNA Rmrp Promotes Mesangial Cell Proliferation and Fibrosis in Diabetic Nephropathy by Modulating the miR-1a-3p/JunD Pathway
title_fullStr Sp1-Induced lncRNA Rmrp Promotes Mesangial Cell Proliferation and Fibrosis in Diabetic Nephropathy by Modulating the miR-1a-3p/JunD Pathway
title_full_unstemmed Sp1-Induced lncRNA Rmrp Promotes Mesangial Cell Proliferation and Fibrosis in Diabetic Nephropathy by Modulating the miR-1a-3p/JunD Pathway
title_short Sp1-Induced lncRNA Rmrp Promotes Mesangial Cell Proliferation and Fibrosis in Diabetic Nephropathy by Modulating the miR-1a-3p/JunD Pathway
title_sort sp1-induced lncrna rmrp promotes mesangial cell proliferation and fibrosis in diabetic nephropathy by modulating the mir-1a-3p/jund pathway
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429906/
https://www.ncbi.nlm.nih.gov/pubmed/34512545
http://dx.doi.org/10.3389/fendo.2021.690784
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