Comprehensive study of altered proteomic landscape in proximal renal tubular epithelial cells in response to calcium oxalate monohydrate crystals

被引:21
作者
Wang, Zhu [1 ]
Li, Ming-xing [2 ]
Xu, Chang-zhi [3 ]
Zhang, Ying [1 ]
Deng, Qiong [1 ]
Sun, Rui [1 ]
Hu, Qi-yi [1 ]
Zhang, Sheng-ping [1 ]
Zhang, Jian-wen [1 ]
Liang, Hui [1 ]
机构
[1] Southern Med Univ, Peoples Hosp Longhua, Dept Urol, Shenzhen 518109, Guangdong, Peoples R China
[2] Southwest Med Univ, Mol Pharmacol Lab, Dept Pharmacol, Sch Pharm, Luzhou 646000, Sichuan, Peoples R China
[3] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Lab Med, Guangzhou 510630, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Calcium oxalate crystal; Kidney stone; Protein expression profile; Renal epithelial cells; INDUCED CYTOTOXICITY; EXPRESSION; PROTEINS; STONES; GENE; PREVALENCE; INJURY;
D O I
10.1186/s12894-020-00709-z
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background Calcium oxalate monohydrate (COM), the major crystalline composition of most kidney stones, induces inflammatory infiltration and injures in renal tubular cells. However, the mechanism of COM-induced toxic effects in renal tubular cells remain ambiguous. The present study aimed to investigate the potential changes in proteomic landscape of proximal renal tubular cells in response to the stimulation of COM crystals. Methods Clinical kidney stone samples were collected and characterized by a stone component analyzer. Three COM-enriched samples were applied to treat human proximal tubular epithelial cells HK-2. The proteomic landscape of COM-crystal treated HK-2 cells was screened by TMT-labeled quantitative proteomics analysis. The differentially expressed proteins (DEPs) were identified by pair-wise analysis. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEPs were performed. Protein interaction networks were identified by STRING database. Results The data of TMT-labeled quantitative proteomic analysis showed that a total of 1141 proteins were differentially expressed in HK-2 cells, of which 699 were up-regulated and 442 were down-regulated. Functional characterization by KEGG, along with GO enrichments, suggests that the DEPs are mainly involved in cellular components and cellular processes, including regulation of actin cytoskeleton, tight junction and focal adhesion. 3 high-degree hub nodes, CFL1, ACTN and MYH9 were identified by STRING analysis. Conclusion These results suggested that calcium oxalate crystal has a significant effect on protein expression profile in human proximal renal tubular epithelial cells.
引用
收藏
页数:12
相关论文
共 41 条
[1]   Nephrolithiasis: Molecular Mechanism of Renal Stone Formation and the Critical Role Played by Modulators [J].
Aggarwal, Kanu Priya ;
Narula, Shifa ;
Kakkar, Monica ;
Tandon, Chanderdeep .
BIOMED RESEARCH INTERNATIONAL, 2013, 2013
[2]   Calcium oxalate crystal adherence to hyaluronan-, osteopontin-, and CD44-expressing injured/regenerating tubular epithelial cells in rat kidneys [J].
Asselman, M ;
Verhulst, A ;
De Broe, ME ;
Verkoelen, CF .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2003, 14 (12) :3155-3166
[3]   Analysis of HK-2 cells exposed to oxalate and calcium oxalate crystals: proteomic insights into the molecular mechanisms of renal injury and stone formation [J].
Chen, Shushang ;
Gao, Xiaofeng ;
Sun, Yinghao ;
Xu, Chuanliang ;
Wang, Linhui ;
Zhou, Tie .
UROLOGICAL RESEARCH, 2010, 38 (01) :7-15
[4]   Mechanisms of human kidney stone formation [J].
Evan, Andrew P. ;
Worcester, Elaine M. ;
Coe, Fredric L. ;
Williams, James, Jr. ;
Lingeman, James E. .
UROLITHIASIS, 2015, 43 (01) :S19-S32
[5]   STRING v9.1: protein-protein interaction networks, with increased coverage and integration [J].
Franceschini, Andrea ;
Szklarczyk, Damian ;
Frankild, Sune ;
Kuhn, Michael ;
Simonovic, Milan ;
Roth, Alexander ;
Lin, Jianyi ;
Minguez, Pablo ;
Bork, Peer ;
von Mering, Christian ;
Jensen, Lars J. .
NUCLEIC ACIDS RESEARCH, 2013, 41 (D1) :D808-D815
[6]   Hes1 promotes cell proliferation and migration by activating Bmi-1 and PTEN/Akt/GSK3β pathway in human colon cancer [J].
Gao, Fei ;
Huang, Wei ;
Zhang, YuQin ;
Tang, ShaoHui ;
Zheng, Lin ;
Ma, Feng ;
Wang, YiMing ;
Tang, Hui ;
Li, Xin .
ONCOTARGET, 2015, 6 (36) :38667-38680
[7]   The FEZ1 gene at chromosome 8p22 encodes a leucine-zipper protein, and its expression is altered in multiple human tumors [J].
Ishii, H ;
Baffa, R ;
Numata, SI ;
Murakumo, Y ;
Rattan, S ;
Inoue, H ;
Mori, M ;
Fidanza, V ;
Alder, H ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (07) :3928-3933
[8]   NADPH Oxidase as a Therapeutic Target for Oxalate Induced Injury in Kidneys [J].
Joshi, Sunil ;
Peck, Ammon B. ;
Khan, Saeed R. .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2013, 2013
[9]   The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the intestinal crypt [J].
Kay, Sophie K. ;
Harrington, Heather A. ;
Shepherd, Sarah ;
Brennan, Keith ;
Dale, Trevor ;
Osborne, James M. ;
Gavaghan, David J. ;
Byrne, Helen M. .
PLOS COMPUTATIONAL BIOLOGY, 2017, 13 (02)
[10]   Role of renal epithelial cells in the initiation of calcium oxalate stones [J].
Khan, SR .
NEPHRON EXPERIMENTAL NEPHROLOGY, 2004, 98 (02) :E55-E60