Differential expression of profibrotic and growth factors in chronic allograft nephropathy

Hilary Hotchkiss, Te Hua Tearina Chu, Wayne W. Hancock, Bernd Schröppel, Matthias Kretzler, Holger Schmid, Yeuxun Liu, Steven Dikman, Enver Akalin

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Background. Chronic allograft nephropathy (CAN) is a multifactorial process, where both immunological and non-immunological factors play roles. Microarrays detect thousands of genes simultaneously. Methods. We have analyzed gene expression profiles of 16 kidney transplant biopsy samples with CAN by high-density oligonucleotide microarrays, comparing to six normal transplant biopsies. Eight CAN biopsies showed nodular arteriolar hyalinization and one was positive for C4d staining. Results. Hierarchical clustering analysis of the 22 biopsies revealed differential gene expression patterns in CAN versus the control biopsies. However, microarray analysis did not reveal differential gene expression patterns in patients with or without arteriolar hyalinization. Fifty percent of the 100 genes with highest hybridization intensities in a C4d positive sample were related to cellular and humoral immune response. Although 212 genes were upregulated a minimum of 1.5-fold, 112 genes were downregulated in CAN samples. There was differential expression of profibrotic and growth factors that while transforming growth factor-β induced factor, thrombospondin 1, and platelet derived growth factor-C were up-regulated, vascular endothelial growth factor, epidermal growth factor, and fibroblast growth factors 1 and 9 were downregulated. Selected differentially expressed genes were confirmed in microdissected samples by real-time quantitative PCR. Immunopathologic examination of biopsies revealed strong TGF-β but decreased glomerular VEGF expression in CAN. Conclusion. Microarrays might be an important tool to uncover the mechanisms of multifactorial diseases, such as CAN.

Original languageEnglish (US)
Pages (from-to)342-349
Number of pages8
JournalTransplantation
Volume81
Issue number3
DOIs
StatePublished - Feb 2006

Keywords

  • Chronic allograft nephropathy
  • GeneChip
  • Kidney transplantation
  • Microarray
  • VEGF

ASJC Scopus subject areas

  • Transplantation

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    Hotchkiss, H., Chu, T. H. T., Hancock, W. W., Schröppel, B., Kretzler, M., Schmid, H., Liu, Y., Dikman, S., & Akalin, E. (2006). Differential expression of profibrotic and growth factors in chronic allograft nephropathy. Transplantation, 81(3), 342-349. https://doi.org/10.1097/01.tp.0000195773.24217.95