title: Identification of Genes Associated with Smad3-dependent Renal Injury by RNA-seq-based Transcriptome Analysis.
abstract: 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.
authors.affiliation: 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.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, China.|SYSU-CMU Shunde International Joint Research Institute, Guangzhou, China.
authors.forename: Yuanyan
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Li Ka Shing Institute of Health Sciences and Department of Medicine &Therapeutics, the Chinese University of Hong Kong, Hong Kong, China.|Shenzhen Research Institute, the Chinese University of Hong Kong, Shenzhen, China.
authors.forename: Xiao R
authors.initials: XR
authors.lastname: Huang
authors.affiliation: Li Ka Shing Institute of Health Sciences and Department of Medicine &Therapeutics, the Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Li Ka Shing Institute of Health Sciences and Department of Medicine &Therapeutics, the Chinese University of Hong Kong, Hong Kong, China.|Shenzhen Research Institute, the Chinese University of Hong Kong, Shenzhen, China.
authors.forename: Hui Y
authors.initials: HY
authors.lastname: Lan
mesh_terms: D000818:Animals; D019295:Computational Biology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D016678:Genome; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D051379:Mice; D018345:Mice, Knockout; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015203:Reproducibility of Results; D015398:Signal Transduction; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D012333:RNA, Messenger; D051900:Smad3 Protein