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Sci Rep. 2015 Dec 9;5:17901. doi: 10.1038/srep17901.

Identification of Genes Associated with Smad3-dependent Renal Injury by RNA-seq-based Transcriptome Analysis.

Zhou Q1,2, Xiong Y3,4, Huang XR2,5, Tang P2, Yu X1, Lan HY2,5.

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Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Li Ka Shing Institute of Health Sciences and Department of Medicine &Therapeutics, the Chinese University of Hong Kong, Hong Kong, China.
State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, China.
SYSU-CMU Shunde International Joint Research Institute, Guangzhou, China.
Shenzhen Research Institute, the Chinese University of Hong Kong, Shenzhen, China.


Transforming growth factor-β/Smad3 signaling plays a critical role in the process of chronic kidney disease (CKD), but targeting Smad3 systematically may cause autoimmune disease by impairing immunity. In this study, we used whole-transcriptome RNA-sequencing to identify the differential gene expression profile, gene ontology, pathways, and alternative splicing related to TGF-β/Smad3 in CKD. To explore common dysregulation of genes associated with Smad3-dependent renal injury, kidney tissues of Smad3 wild-type and knockout mice with immune (anti-glomerular basement membrane glomerulonephritis) and non-immune (obstructive nephropathy)-mediated CKD were used for RNA-sequencing analysis. Totally 1922 differentially expressed genes (DEGs) were commonly found in these CKD models. The up-regulated genes are inflammatory and immune response associated, while decreased genes are material or electron transportation and metabolism related. Only 9 common DEGs were found to be Smad3-dependent in two models, including 6 immunoglobulin genes (Ighg1, Ighg2c, Igkv12-41, Ighv14-3, Ighv5-6 and Ighg2b) and 3 metabolic genes (Ugt2b37, Slc22a19, and Mfsd2a). Our results identify transcriptomes associated with renal injury may represent a common mechanism for the pathogenesis of CKD and reveal novel Smad3 associated transcriptomes in the development of CKD.

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