Microarray and bioinformatic detection of novel and established genes expressed in experimental anti-Thy1 nephritis

Denise M. Sadlier, Xuesong Ouyang, Blaithin McMahon, Wei Mu, Ryuji Ohashi, Karen Rodgers, David Murray, Takahiko Nakagawa, Catherine Godson, Peter Doran, Hugh R. Brady, Rick J. Johnson

Research output: Contribution to journalArticle

Abstract

Background. Microarray technology is a powerful tool that can probe the molecular pathogenesis of renal injury. In this present study microarray analysis was used to monitor serial changes in the renal transcriptome of a rat model of mesangial proliferative glomerulonephritis. Administration of anti-Thy1 antibody results in phases of acute mesangial injury (day 2), cell proliferation (day 5), matrix expansion (days 5 and 7), and subsequent healing (day 14). Methods. Using Affymetrix (RAE230A) microarrays coupled with sequential primary biologic function-focused and secondary "baited" global cluster analysis, a cohort of established and putative novel modulators of mesangial cell turnover was identified. Results. Cluster analysis of proliferative genes identified a number of gene expression profiles. The most striking pattern was increased gene expression at day 5, a cluster that included platelet-derived growth factor (PDGF), cyclins and transforming growth factor-β (TGF-β). The gene expression patterns identified by primary focused cluster analysis were used as bioinformatic bait and resulted in the identification of novel families of genes such as the S100 family. The expression of established and novel genes was confirmed using reverse transcription-polymerase chain reaction (RT-PCR). Next, in vivo gene expression was compared to PDGF-stimulated mesangial cells in vitro revealing similar patterns of dysregulation. Conclusion. Transcriptomic analysis defined both known and novel molecules involved in mesangial cell proliferation in vitro and in vivo and defined a panel of molecules that are potential contributors to mesangial cell dysfunction in glomerular disease.

Original languageEnglish (US)
Pages (from-to)2542-2561
Number of pages20
JournalKidney International
Volume68
Issue number6
DOIs
Publication statusPublished - Dec 2005
Externally publishedYes

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Keywords

  • Anti-Thy1 nephritis
  • Enigma
  • IgA nephropathy (IgAN)
  • Mesangial cell proliferation
  • Platelet-derived growth factor (PDGF)
  • Transforming growth factor beta (TGF-β)

ASJC Scopus subject areas

  • Nephrology

Cite this

Sadlier, D. M., Ouyang, X., McMahon, B., Mu, W., Ohashi, R., Rodgers, K., ... Johnson, R. J. (2005). Microarray and bioinformatic detection of novel and established genes expressed in experimental anti-Thy1 nephritis. Kidney International, 68(6), 2542-2561. https://doi.org/10.1111/j.1523-1755.2005.00661.x