Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway

Progressive albuminuria is the primary clinical symptom of diabetic nephropathy (DN), leading to a gradual decline in kidney function. DLX6-AS1 was the first reported long non-coding RNA (lncRNA) to participate in organogenesis and play crucial roles in the brain or neural cell development. Herein,...

Descripción completa

Detalles Bibliográficos
Autores principales: Guo, Jia, Zheng, Wen, Liu, Yong, Zhou, Mengwen, Shi, Yan, Lei, Min, Zhang, Chaojie, Liu, Zhangsuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9975222/
https://www.ncbi.nlm.nih.gov/pubmed/36854759
http://dx.doi.org/10.1038/s41419-023-05695-2
_version_ 1784898828001869824
author Guo, Jia
Zheng, Wen
Liu, Yong
Zhou, Mengwen
Shi, Yan
Lei, Min
Zhang, Chaojie
Liu, Zhangsuo
author_facet Guo, Jia
Zheng, Wen
Liu, Yong
Zhou, Mengwen
Shi, Yan
Lei, Min
Zhang, Chaojie
Liu, Zhangsuo
author_sort Guo, Jia
collection PubMed
description Progressive albuminuria is the primary clinical symptom of diabetic nephropathy (DN), leading to a gradual decline in kidney function. DLX6-AS1 was the first reported long non-coding RNA (lncRNA) to participate in organogenesis and play crucial roles in the brain or neural cell development. Herein, we investigated the DLX6-AS1 (Dlx6-os1 in mice) role in DN pathogenesis. We found that DLX6-AS1 expression in DN patients correlated with the extent of albuminuria. Dlx6-os1 overexpression induced cellular damage and inflammatory responses in cultured podocytes through miR-346-mediated regulation of the GSK-3β pathway. In various established diabetic and newly developed knockout mouse models, Dlx6-os1 knockdown/knockout significantly reduced podocyte injury and albuminuria. The Dlx6-os1 effects were remarkably modulated by miR-346 mimics or mutants and significantly diminished in podocyte-specific GSK-3β-knockout mice. Thus, DLX6-AS1 (Dlx6-os1) promotes DN development by accelerating podocyte injury and inflammation through the upregulation of the GSK-3β pathway, providing a novel molecular target for DN therapy.
format Online
Article
Text
id pubmed-9975222
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-99752222023-03-02 Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway Guo, Jia Zheng, Wen Liu, Yong Zhou, Mengwen Shi, Yan Lei, Min Zhang, Chaojie Liu, Zhangsuo Cell Death Dis Article Progressive albuminuria is the primary clinical symptom of diabetic nephropathy (DN), leading to a gradual decline in kidney function. DLX6-AS1 was the first reported long non-coding RNA (lncRNA) to participate in organogenesis and play crucial roles in the brain or neural cell development. Herein, we investigated the DLX6-AS1 (Dlx6-os1 in mice) role in DN pathogenesis. We found that DLX6-AS1 expression in DN patients correlated with the extent of albuminuria. Dlx6-os1 overexpression induced cellular damage and inflammatory responses in cultured podocytes through miR-346-mediated regulation of the GSK-3β pathway. In various established diabetic and newly developed knockout mouse models, Dlx6-os1 knockdown/knockout significantly reduced podocyte injury and albuminuria. The Dlx6-os1 effects were remarkably modulated by miR-346 mimics or mutants and significantly diminished in podocyte-specific GSK-3β-knockout mice. Thus, DLX6-AS1 (Dlx6-os1) promotes DN development by accelerating podocyte injury and inflammation through the upregulation of the GSK-3β pathway, providing a novel molecular target for DN therapy. Nature Publishing Group UK 2023-02-28 /pmc/articles/PMC9975222/ /pubmed/36854759 http://dx.doi.org/10.1038/s41419-023-05695-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Guo, Jia
Zheng, Wen
Liu, Yong
Zhou, Mengwen
Shi, Yan
Lei, Min
Zhang, Chaojie
Liu, Zhangsuo
Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway
title Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway
title_full Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway
title_fullStr Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway
title_full_unstemmed Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway
title_short Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway
title_sort long non-coding rna dlx6-as1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the mir-346/gsk-3β signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9975222/
https://www.ncbi.nlm.nih.gov/pubmed/36854759
http://dx.doi.org/10.1038/s41419-023-05695-2
work_keys_str_mv AT guojia longnoncodingrnadlx6as1isthekeymediatorofglomerularpodocyteinjuryandalbuminuriaindiabeticnephropathybytargetingthemir346gsk3bsignalingpathway
AT zhengwen longnoncodingrnadlx6as1isthekeymediatorofglomerularpodocyteinjuryandalbuminuriaindiabeticnephropathybytargetingthemir346gsk3bsignalingpathway
AT liuyong longnoncodingrnadlx6as1isthekeymediatorofglomerularpodocyteinjuryandalbuminuriaindiabeticnephropathybytargetingthemir346gsk3bsignalingpathway
AT zhoumengwen longnoncodingrnadlx6as1isthekeymediatorofglomerularpodocyteinjuryandalbuminuriaindiabeticnephropathybytargetingthemir346gsk3bsignalingpathway
AT shiyan longnoncodingrnadlx6as1isthekeymediatorofglomerularpodocyteinjuryandalbuminuriaindiabeticnephropathybytargetingthemir346gsk3bsignalingpathway
AT leimin longnoncodingrnadlx6as1isthekeymediatorofglomerularpodocyteinjuryandalbuminuriaindiabeticnephropathybytargetingthemir346gsk3bsignalingpathway
AT zhangchaojie longnoncodingrnadlx6as1isthekeymediatorofglomerularpodocyteinjuryandalbuminuriaindiabeticnephropathybytargetingthemir346gsk3bsignalingpathway
AT liuzhangsuo longnoncodingrnadlx6as1isthekeymediatorofglomerularpodocyteinjuryandalbuminuriaindiabeticnephropathybytargetingthemir346gsk3bsignalingpathway

Ejemplares similares