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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computational Biology
  • Disease Models, Animal
  • Gene Expression Profiling*
  • Gene Expression Regulation*
  • Gene Ontology
  • Genome
  • Genomics
  • High-Throughput Nucleotide Sequencing
  • Mice
  • Mice, Knockout
  • RNA Splicing
  • RNA, Messenger / genetics
  • Renal Insufficiency, Chronic / genetics*
  • Renal Insufficiency, Chronic / metabolism*
  • Renal Insufficiency, Chronic / pathology
  • Reproducibility of Results
  • Signal Transduction
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism*
  • Transcriptome*

Substances

  • RNA, Messenger
  • Smad3 Protein