title: Proteomic and phosphoproteomic analysis of renal cortex in a salt-load rat model of advanced kidney damage.
abstract: Salt plays an essential role in the progression of chronic kidney disease and hypertension. However, the mechanisms underlying pathogenesis of salt-induced kidney damage remain largely unknown. Here, Sprague-Dawley rats, that underwent 5/6 nephrectomy (5/6Nx, a model of advanced kidney damage) or sham operation, were treated for 2 weeks with a normal or high-salt diet. We employed aTiO2enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for proteomic and phosphoproteomic profiling of the renal cortex. We found 318 proteins differentially expressed in 5/6Nx group relative to sham group, and 310 proteins significantly changed in response to salt load in 5/6Nx animals. Totally, 1810 unique phosphopeptides corresponding to 550 phosphoproteins were identified. We identified 113 upregulated and 84 downregulated phosphopeptides in 5/6Nx animals relative to sham animals. Salt load induced 78 upregulated and 91 downregulated phosphopeptides in 5/6Nx rats. The differentially expressed phospholproteins are important transporters, structural molecules, and receptors. Protein-protein interaction analysis revealed that the differentially phosphorylated proteins in 5/6Nx group, Polr2a, Srrm1, Gsta2 and Pxn were the most linked. Salt-induced differential phosphoproteins, Myh6, Lmna and Des were the most linked. Altered phosphorylation levels of lamin A and phospholamban were validated. This study will provide new insight into pathogenetic mechanisms of chronic kidney disease and salt sensitivity.
authors: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Shaoling
authors: S
authors: Jiang
authors: The First People's Foshan Hospital, Foshan, China.
authors: Hanchang
authors: H
authors: He
authors: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Lishan
authors: L
authors: Tan
authors: Division of Nephrology, First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, P.R. China.
authors: Liangliang
authors: L
authors: Wang
authors: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Zhengxiu
authors: Z
authors: Su
authors: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Yufeng
authors: Y
authors: Liu
authors: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Hongguo
authors: H
authors: Zhu
authors: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Menghuan
authors: M
authors: Zhang
authors: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Fan Fan
authors: FF
authors: Hou
authors: State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Aiqing
authors: A
authors: Li
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D004032:Diet / Q000379:methods; D004195:Disease Models, Animal; D007672:Kidney Cortex / Q000473:pathology*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D017207:Rats, Sprague-Dawley; D012492:Salts / Q000008:administration & dosage*; D053719:Tandem Mass Spectrometry
chemical_list: D020543:Proteome; D012492:Salts