Comprehensive study of altered proteomic landscape in proximal renal tubular epithelial cells in response to calcium oxa

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RESEARCH ARTICLE

Open Access

Comprehensive study of altered proteomic landscape in proximal renal tubular epithelial cells in response to calcium oxalate monohydrate crystals Zhu Wang1*†, Ming-xing Li2†, Chang-zhi Xu3†, Ying Zhang1, Qiong Deng1, Rui Sun1, Qi-yi Hu1, Sheng-ping Zhang1, Jian-wen Zhang1 and Hui Liang1*

Abstract 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. Keywords: Calcium oxalate crystal, Kidney stone, Protein expression profile, Renal epithelial cells

* Correspondence: [email protected]; [email protected] † Zhu Wang, Ming-xing Li and Chang-zhi Xu contributed equally to this work. 1 Department of Urology, People’s Hospital of Longhua, Southern Medical University, Shenzhen 518109, Guangdong, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'