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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Autores principales: Jiayi Wan, Mingyang Hu, Ziming Jiang, Dongwei Liu, Shaokang Pan, Sijie Zhou, Zhangsuo Liu
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Publicado: Frontiers Media S.A. 2021
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spelling 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 DOAJ
collection DOAJ
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
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