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Inhibition of the lncRNA MIAT prevents podocyte injury and mitotic catastrophe in diabetic nephropathy
Podocyte damage is strongly associated with the progression of diabetic nephropathy. Mitotic catastrophe plays an essential role in accelerating podocyte loss and detachment from the glomerular basement membrane. In the current study, we observed that the long non-coding RNA (lncRNA) MIAT was notice...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956887/ https://www.ncbi.nlm.nih.gov/pubmed/35402074 http://dx.doi.org/10.1016/j.omtn.2022.03.001 |
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author | Wang, Ziyang Chang, Ying Liu, Yue Liu, Bing Zhen, Junhui Li, Xiaobing Lin, Jiangong Yu, Qun Lv, Zhimei Wang, Rong |
author_facet | Wang, Ziyang Chang, Ying Liu, Yue Liu, Bing Zhen, Junhui Li, Xiaobing Lin, Jiangong Yu, Qun Lv, Zhimei Wang, Rong |
author_sort | Wang, Ziyang |
collection | PubMed |
description | Podocyte damage is strongly associated with the progression of diabetic nephropathy. Mitotic catastrophe plays an essential role in accelerating podocyte loss and detachment from the glomerular basement membrane. In the current study, we observed that the long non-coding RNA (lncRNA) MIAT was noticeably upregulated in the plasma and kidney tissues of patients with diabetic nephropathy, and this upregulation was accompanied by higher albumin/creatinine ratios and serum creatinine levels. By generating CRISPR-Cas9 Miat-knockout (KO) mice in vivo and employing vectors in vitro, we found that the depletion of Miat expression significantly restored slit-diaphragm integrity, attenuated foot process effacement, prevented dedifferentiation, and suppressed mitotic catastrophe in podocytes during hyperglycemia. The mechanistic investigation revealed that Miat increased Sox4 expression and subsequently regulated p53 ubiquitination and acetylation, thereby inhibiting the downstream factors CyclinB/cdc2 by enhancing p21(cip1/waf1) activity, and that Miat interacted with Sox4 by sponging miR-130b-3p. Additionally, the inhibition of miR-130b-3p with an antagomir in vivo effectively enhanced glomerular podocyte injury and mitotic dysfunction, eventually exacerbating proteinuria. Based on these findings, MIAT may represent a therapeutic target for diabetic nephropathy. |
format | Online Article Text |
id | pubmed-8956887 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-89568872022-04-07 Inhibition of the lncRNA MIAT prevents podocyte injury and mitotic catastrophe in diabetic nephropathy Wang, Ziyang Chang, Ying Liu, Yue Liu, Bing Zhen, Junhui Li, Xiaobing Lin, Jiangong Yu, Qun Lv, Zhimei Wang, Rong Mol Ther Nucleic Acids Original Article Podocyte damage is strongly associated with the progression of diabetic nephropathy. Mitotic catastrophe plays an essential role in accelerating podocyte loss and detachment from the glomerular basement membrane. In the current study, we observed that the long non-coding RNA (lncRNA) MIAT was noticeably upregulated in the plasma and kidney tissues of patients with diabetic nephropathy, and this upregulation was accompanied by higher albumin/creatinine ratios and serum creatinine levels. By generating CRISPR-Cas9 Miat-knockout (KO) mice in vivo and employing vectors in vitro, we found that the depletion of Miat expression significantly restored slit-diaphragm integrity, attenuated foot process effacement, prevented dedifferentiation, and suppressed mitotic catastrophe in podocytes during hyperglycemia. The mechanistic investigation revealed that Miat increased Sox4 expression and subsequently regulated p53 ubiquitination and acetylation, thereby inhibiting the downstream factors CyclinB/cdc2 by enhancing p21(cip1/waf1) activity, and that Miat interacted with Sox4 by sponging miR-130b-3p. Additionally, the inhibition of miR-130b-3p with an antagomir in vivo effectively enhanced glomerular podocyte injury and mitotic dysfunction, eventually exacerbating proteinuria. Based on these findings, MIAT may represent a therapeutic target for diabetic nephropathy. American Society of Gene & Cell Therapy 2022-03-08 /pmc/articles/PMC8956887/ /pubmed/35402074 http://dx.doi.org/10.1016/j.omtn.2022.03.001 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Wang, Ziyang Chang, Ying Liu, Yue Liu, Bing Zhen, Junhui Li, Xiaobing Lin, Jiangong Yu, Qun Lv, Zhimei Wang, Rong Inhibition of the lncRNA MIAT prevents podocyte injury and mitotic catastrophe in diabetic nephropathy |
title | Inhibition of the lncRNA MIAT prevents podocyte injury and mitotic catastrophe in diabetic nephropathy |
title_full | Inhibition of the lncRNA MIAT prevents podocyte injury and mitotic catastrophe in diabetic nephropathy |
title_fullStr | Inhibition of the lncRNA MIAT prevents podocyte injury and mitotic catastrophe in diabetic nephropathy |
title_full_unstemmed | Inhibition of the lncRNA MIAT prevents podocyte injury and mitotic catastrophe in diabetic nephropathy |
title_short | Inhibition of the lncRNA MIAT prevents podocyte injury and mitotic catastrophe in diabetic nephropathy |
title_sort | inhibition of the lncrna miat prevents podocyte injury and mitotic catastrophe in diabetic nephropathy |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956887/ https://www.ncbi.nlm.nih.gov/pubmed/35402074 http://dx.doi.org/10.1016/j.omtn.2022.03.001 |
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