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JMJD1A/NR4A1 Signaling Regulates the Procession of Renal Tubular Epithelial Interstitial Fibrosis Induced by AGEs in HK-2

Diabetic kidney disease (DKD) is one of the most serious complications of diabetic patients. Advanced glycation end products (AGEs) induce epithelial-mesenchymal transformation (EMT) of renal tubular epithelial cells (HK-2), resulting in renal tubulointerstitial fibrosis. However, the underlying epi...

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Autores principales: Wang, Shaoting, Zuo, Anna, Jiang, Weiqiang, Xie, Jiarun, Lin, Haoyu, Sun, Wei, Zhao, Min, Xia, Jinjin, Shao, Junqiao, Zhao, Xiaoshan, Liang, Donghui, Yang, Aicheng, Sun, Jia, Wang, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850412/
https://www.ncbi.nlm.nih.gov/pubmed/35186975
http://dx.doi.org/10.3389/fmed.2021.807694
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author Wang, Shaoting
Zuo, Anna
Jiang, Weiqiang
Xie, Jiarun
Lin, Haoyu
Sun, Wei
Zhao, Min
Xia, Jinjin
Shao, Junqiao
Zhao, Xiaoshan
Liang, Donghui
Yang, Aicheng
Sun, Jia
Wang, Ming
author_facet Wang, Shaoting
Zuo, Anna
Jiang, Weiqiang
Xie, Jiarun
Lin, Haoyu
Sun, Wei
Zhao, Min
Xia, Jinjin
Shao, Junqiao
Zhao, Xiaoshan
Liang, Donghui
Yang, Aicheng
Sun, Jia
Wang, Ming
author_sort Wang, Shaoting
collection PubMed
description Diabetic kidney disease (DKD) is one of the most serious complications of diabetic patients. Advanced glycation end products (AGEs) induce epithelial-mesenchymal transformation (EMT) of renal tubular epithelial cells (HK-2), resulting in renal tubulointerstitial fibrosis. However, the underlying epigenetic mechanisms remain to be further investigated. In this work, we investigated the functional role of JMJD1A involved in DKD progression. The molecular mechanism study was performed in AGEs-induced HK-2 cells by gene expression analysis, RNA sequencing (RNA-seq), and JMJD1A lentiviral knockdown and overexpression particle transfection. The results showed that AGEs could upregulate JMJD1A, and the expressions of related fibrotic factor were also increased. At the same time, in the DKD animal model induced by unilateral nephrectomy plus streptozotocin (STZ), IHC immunohistochemical staining showed that compared with the control group, the expressions of JMJD1A, FN, and COL1 in the model group were all increased, masson staining results also show that the model group has typical fibrotic changes. This is consistent with the results of our in vitro experiments. In order to determine the downstream pathway, we screened out JMJD1A downstream transcription factors by RNA-seq. Further analysis showed that JMJD1A overexpression could accelerate the progression of AGEs-induced renal fibrosis by reducing the expression of NR4A1 in HK-2 cells. Meanwhile, NR4A1 inhibitor can promote the expression of fibrosis-related factors such as VIM, a-SMA in HK-2 cells, and aggravate the process of fibrosis. Taken together, JMJD1A/NR4A1 signaling can regulate the procession of renal tubular epithelial interstitial fibrosis induced by AGEs in HK-2.
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spelling pubmed-88504122022-02-18 JMJD1A/NR4A1 Signaling Regulates the Procession of Renal Tubular Epithelial Interstitial Fibrosis Induced by AGEs in HK-2 Wang, Shaoting Zuo, Anna Jiang, Weiqiang Xie, Jiarun Lin, Haoyu Sun, Wei Zhao, Min Xia, Jinjin Shao, Junqiao Zhao, Xiaoshan Liang, Donghui Yang, Aicheng Sun, Jia Wang, Ming Front Med (Lausanne) Medicine Diabetic kidney disease (DKD) is one of the most serious complications of diabetic patients. Advanced glycation end products (AGEs) induce epithelial-mesenchymal transformation (EMT) of renal tubular epithelial cells (HK-2), resulting in renal tubulointerstitial fibrosis. However, the underlying epigenetic mechanisms remain to be further investigated. In this work, we investigated the functional role of JMJD1A involved in DKD progression. The molecular mechanism study was performed in AGEs-induced HK-2 cells by gene expression analysis, RNA sequencing (RNA-seq), and JMJD1A lentiviral knockdown and overexpression particle transfection. The results showed that AGEs could upregulate JMJD1A, and the expressions of related fibrotic factor were also increased. At the same time, in the DKD animal model induced by unilateral nephrectomy plus streptozotocin (STZ), IHC immunohistochemical staining showed that compared with the control group, the expressions of JMJD1A, FN, and COL1 in the model group were all increased, masson staining results also show that the model group has typical fibrotic changes. This is consistent with the results of our in vitro experiments. In order to determine the downstream pathway, we screened out JMJD1A downstream transcription factors by RNA-seq. Further analysis showed that JMJD1A overexpression could accelerate the progression of AGEs-induced renal fibrosis by reducing the expression of NR4A1 in HK-2 cells. Meanwhile, NR4A1 inhibitor can promote the expression of fibrosis-related factors such as VIM, a-SMA in HK-2 cells, and aggravate the process of fibrosis. Taken together, JMJD1A/NR4A1 signaling can regulate the procession of renal tubular epithelial interstitial fibrosis induced by AGEs in HK-2. Frontiers Media S.A. 2022-02-03 /pmc/articles/PMC8850412/ /pubmed/35186975 http://dx.doi.org/10.3389/fmed.2021.807694 Text en Copyright © 2022 Wang, Zuo, Jiang, Xie, Lin, Sun, Zhao, Xia, Shao, Zhao, Liang, Yang, Sun and Wang. 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 Medicine
Wang, Shaoting
Zuo, Anna
Jiang, Weiqiang
Xie, Jiarun
Lin, Haoyu
Sun, Wei
Zhao, Min
Xia, Jinjin
Shao, Junqiao
Zhao, Xiaoshan
Liang, Donghui
Yang, Aicheng
Sun, Jia
Wang, Ming
JMJD1A/NR4A1 Signaling Regulates the Procession of Renal Tubular Epithelial Interstitial Fibrosis Induced by AGEs in HK-2
title JMJD1A/NR4A1 Signaling Regulates the Procession of Renal Tubular Epithelial Interstitial Fibrosis Induced by AGEs in HK-2
title_full JMJD1A/NR4A1 Signaling Regulates the Procession of Renal Tubular Epithelial Interstitial Fibrosis Induced by AGEs in HK-2
title_fullStr JMJD1A/NR4A1 Signaling Regulates the Procession of Renal Tubular Epithelial Interstitial Fibrosis Induced by AGEs in HK-2
title_full_unstemmed JMJD1A/NR4A1 Signaling Regulates the Procession of Renal Tubular Epithelial Interstitial Fibrosis Induced by AGEs in HK-2
title_short JMJD1A/NR4A1 Signaling Regulates the Procession of Renal Tubular Epithelial Interstitial Fibrosis Induced by AGEs in HK-2
title_sort jmjd1a/nr4a1 signaling regulates the procession of renal tubular epithelial interstitial fibrosis induced by ages in hk-2
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850412/
https://www.ncbi.nlm.nih.gov/pubmed/35186975
http://dx.doi.org/10.3389/fmed.2021.807694
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