scholarly journals Lysine Acetylation in the Proteome of Renal Tubular Epithelial Cells in Diabetic Nephropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiayi Wan ◽  
Mingyang Hu ◽  
Ziming Jiang ◽  
Dongwei Liu ◽  
Shaokang Pan ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Epithelial Cells ◽  
High Resolution Mass Spectrometry ◽  
Microvascular Complications ◽  
Lysine Acetylation ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Renal Tubular

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.

Role of Complement 3 in TNF-α-Induced Mesenchymal Transition of Renal Tubular Epithelial Cells In Vitro

2012 ◽  
Vol 54 (1) ◽  
pp. 92-100 ◽  
Author(s):  
Jianxin Wan ◽  
Xueli Zhou ◽  
Jiong Cui ◽  
Zhenhuan Zou ◽  
Yanfang Xu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Mesenchymal Transition ◽  
Complement 3 ◽  
Tnf Α ◽  
Renal Tubular

scholarly journals JAK2/Y343/STAT5 signaling axis is required for erythropoietin-mediated protection against ischemic injury in primary renal tubular epithelial cells

2008 ◽  
Vol 295 (6) ◽  
pp. F1689-F1695 ◽  
Author(s):  
A. C. Breggia ◽  
D. M. Wojchowski ◽  
J. Himmelfarb
Keyword(s):  
Epithelial Cells ◽  
Tissue Injury ◽  
Ischemic Injury ◽  
Erythropoietin Receptor ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Primary Mouse ◽  
Signaling Axis ◽  
Renal Tubular

Erythropoietin has emerged as a potential therapy for the treatment of ischemic tissue injury. In erythroid cells, the JAK2/Y343/STAT5 signaling axis has been shown to be necessary for stress but not steady-state erythropoiesis. The requirement for STAT5 activation in erythropoietin-mediated protection from ischemic injury has not been well-studied. To answer this question, we induced reproducible necrotic ischemic injury in primary mouse renal tubular epithelial cells (RTEC) in vitro. Using RTEC from erythropoietin receptor mutant mice with differential STAT5 signaling capabilities, we demonstrated first, that EPO administration either before or during injury significantly protects against mild-moderate but not severe necrotic cell death; and second, the JAK2/Y343/STAT5 signaling axis is required for protection against ischemic injury in primary mouse RTEC. In addition, we identified Pim-3, a prosurvival STAT5 target gene, as responsive to EPO in the noninjured kidney both in vitro and in vivo.

Cross talk between primary human renal tubular cells and endothelial cells in cocultures

2012 ◽  
Vol 302 (8) ◽  
pp. F1055-F1062 ◽  
Author(s):  
Farah Tasnim ◽  
Daniele Zink
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Renal Disease ◽  
Cross Talk ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Tubular Cells ◽  
Renal Tubular

Interactions between renal tubular epithelial cells and adjacent endothelial cells are essential for normal renal functions but also play important roles in renal disease and repair. Here, we investigated cocultures of human primary renal proximal tubular cells (HPTC) and human primary endothelial cells to address the cross talk between these cell types. HPTC showed improved proliferation, marker gene expression, and enzyme activity in cocultures. Also, the long-term maintenance of epithelia formed by HPTC was improved, which was due to the secretion of transforming growth factor-β1 and its antagonist α2-macroglobulin. HPTC induced endothelial cells to secrete increased amounts of these factors, which balanced each other functionally and only displayed in combination the observed positive effects. In addition, in the presence of HPTC endothelial cells expressed increased amounts of hepatocyte growth factor and vascular endothelial growth factor, which have well-characterized effects on renal tubular epithelial cells as well as on endothelial cells. Together, the results showed that HPTC stimulated endothelial cells to express a functionally balanced combination of various factors, which in turn improved the performance of HPTC. The results give new insights into the cross talk between renal epithelial and endothelial cells and suggest that cocultures could be also useful models for the analysis of cellular communication in renal disease and repair. Furthermore, the characterization of defined microenvironments, which positively affect HPTC, will be helpful for improving the performance of this cell type in in vitro applications including in vitro toxicology and kidney tissue engineering.

Sign in / Sign up

Export Citation Format

Share Document