Lysine Acetylation in the Proteome of Renal Tubular Epithelial Cells in Diabetic Nephropathy
Diabetic nephropathy is considered one of the most common microvascular complications of diabetes and the pathophysiology involves multiple factors. Progressive diabetic nephropathy is believed to be related to the structure and function of the tubular epithelial cells in the kidney. However, the ro...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:c9084f39fab849168b9b2e9d58d2098e2021-12-01T03:33:21ZLysine Acetylation in the Proteome of Renal Tubular Epithelial Cells in Diabetic Nephropathy1664-802110.3389/fgene.2021.767135https://doaj.org/article/c9084f39fab849168b9b2e9d58d2098e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.767135/fullhttps://doaj.org/toc/1664-8021Diabetic nephropathy is considered one of the most common microvascular complications of diabetes and the pathophysiology involves multiple factors. Progressive diabetic nephropathy is believed to be related to the structure and function of the tubular epithelial cells in the kidney. However, the role of lysine acetylation in lesions of the renal tubular epithelial cells arising from hyperglycemia is poorly understood. Consequently, in this study, we cultured mouse renal tubular epithelial cells in vitro under high glucose conditions and analyzed the acetylation levels of proteins by liquid chromatography-high-resolution mass spectrometry. We identified 48 upregulated proteins and downregulated 86 proteins. In addition, we identified 113 sites with higher acetylation levels and 374 sites with lower acetylation levels. Subcellular localization analysis showed that the majority of the acetylated proteins were located in the mitochondria (43.17%), nucleus (28.57%) and cytoplasm (16.19%). Enrichment analysis indicated that these acetylated proteins are primarily associated with oxidative phosphorylation, the citrate cycle (TCA cycle), metabolic pathways and carbon metabolism. In addition, we used the MCODE plug-in and the cytoHubba plug-in in Cytoscape software to analyze the PPI network and displayed the first four most compact MOCDEs and the top 10 hub genes from the differentially expressed proteins between global and acetylated proteomes. Finally, we extracted 37 conserved motifs from 4915 acetylated peptides. Collectively, this comprehensive analysis of the proteome reveals novel insights into the role of lysine acetylation in tubular epithelial cells and may make a valuable contribution towards the identification of the pathological mechanisms of diabetic nephropathy.Jiayi WanJiayi WanJiayi WanJiayi WanMingyang HuMingyang HuMingyang HuMingyang HuZiming JiangZiming JiangZiming JiangZiming JiangDongwei LiuDongwei LiuDongwei LiuDongwei LiuShaokang PanShaokang PanShaokang PanShaokang PanSijie ZhouSijie ZhouSijie ZhouSijie ZhouZhangsuo LiuZhangsuo LiuZhangsuo LiuZhangsuo LiuFrontiers Media S.A.articleproteomelysine acetylationrenal tubular epithelial cellsdiabetic nephropathyacetyltransferaseGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021) |
institution |
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language |
EN |
topic |
proteome lysine acetylation renal tubular epithelial cells diabetic nephropathy acetyltransferase Genetics QH426-470 |
spellingShingle |
proteome lysine acetylation renal tubular epithelial cells diabetic nephropathy acetyltransferase Genetics QH426-470 Jiayi Wan Jiayi Wan Jiayi Wan Jiayi Wan Mingyang Hu Mingyang Hu Mingyang Hu Mingyang Hu Ziming Jiang Ziming Jiang Ziming Jiang Ziming Jiang Dongwei Liu Dongwei Liu Dongwei Liu Dongwei Liu Shaokang Pan Shaokang Pan Shaokang Pan Shaokang Pan Sijie Zhou Sijie Zhou Sijie Zhou Sijie Zhou Zhangsuo Liu Zhangsuo Liu Zhangsuo Liu Zhangsuo Liu Lysine Acetylation in the Proteome of Renal Tubular Epithelial Cells in Diabetic Nephropathy |
description |
Diabetic nephropathy is considered one of the most common microvascular complications of diabetes and the pathophysiology involves multiple factors. Progressive diabetic nephropathy is believed to be related to the structure and function of the tubular epithelial cells in the kidney. However, the role of lysine acetylation in lesions of the renal tubular epithelial cells arising from hyperglycemia is poorly understood. Consequently, in this study, we cultured mouse renal tubular epithelial cells in vitro under high glucose conditions and analyzed the acetylation levels of proteins by liquid chromatography-high-resolution mass spectrometry. We identified 48 upregulated proteins and downregulated 86 proteins. In addition, we identified 113 sites with higher acetylation levels and 374 sites with lower acetylation levels. Subcellular localization analysis showed that the majority of the acetylated proteins were located in the mitochondria (43.17%), nucleus (28.57%) and cytoplasm (16.19%). Enrichment analysis indicated that these acetylated proteins are primarily associated with oxidative phosphorylation, the citrate cycle (TCA cycle), metabolic pathways and carbon metabolism. In addition, we used the MCODE plug-in and the cytoHubba plug-in in Cytoscape software to analyze the PPI network and displayed the first four most compact MOCDEs and the top 10 hub genes from the differentially expressed proteins between global and acetylated proteomes. Finally, we extracted 37 conserved motifs from 4915 acetylated peptides. Collectively, this comprehensive analysis of the proteome reveals novel insights into the role of lysine acetylation in tubular epithelial cells and may make a valuable contribution towards the identification of the pathological mechanisms of diabetic nephropathy. |
format |
article |
author |
Jiayi Wan Jiayi Wan Jiayi Wan Jiayi Wan Mingyang Hu Mingyang Hu Mingyang Hu Mingyang Hu Ziming Jiang Ziming Jiang Ziming Jiang Ziming Jiang Dongwei Liu Dongwei Liu Dongwei Liu Dongwei Liu Shaokang Pan Shaokang Pan Shaokang Pan Shaokang Pan Sijie Zhou Sijie Zhou Sijie Zhou Sijie Zhou Zhangsuo Liu Zhangsuo Liu Zhangsuo Liu Zhangsuo Liu |
author_facet |
Jiayi Wan Jiayi Wan Jiayi Wan Jiayi Wan Mingyang Hu Mingyang Hu Mingyang Hu Mingyang Hu Ziming Jiang Ziming Jiang Ziming Jiang Ziming Jiang Dongwei Liu Dongwei Liu Dongwei Liu Dongwei Liu Shaokang Pan Shaokang Pan Shaokang Pan Shaokang Pan Sijie Zhou Sijie Zhou Sijie Zhou Sijie Zhou Zhangsuo Liu Zhangsuo Liu Zhangsuo Liu Zhangsuo Liu |
author_sort |
Jiayi Wan |
title |
Lysine Acetylation in the Proteome of Renal Tubular Epithelial Cells in Diabetic Nephropathy |
title_short |
Lysine Acetylation in the Proteome of Renal Tubular Epithelial Cells in Diabetic Nephropathy |
title_full |
Lysine Acetylation in the Proteome of Renal Tubular Epithelial Cells in Diabetic Nephropathy |
title_fullStr |
Lysine Acetylation in the Proteome of Renal Tubular Epithelial Cells in Diabetic Nephropathy |
title_full_unstemmed |
Lysine Acetylation in the Proteome of Renal Tubular Epithelial Cells in Diabetic Nephropathy |
title_sort |
lysine acetylation in the proteome of renal tubular epithelial cells in diabetic nephropathy |
publisher |
Frontiers Media S.A. |
publishDate |
2021 |
url |
https://doaj.org/article/c9084f39fab849168b9b2e9d58d2098e |
work_keys_str_mv |
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