Differential expression of profibrotic and growth factors in chronic allograft nephropathy.
BACKGROUND
Chronic allograft nephropathy (CAN) is a multifactorial process, where both immunological and nonimmunological 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-beta 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-beta but decreased glomerular VEGF expression in CAN.


CONCLUSIONS
Microarrays might be an important tool to uncover the mechanisms of multifactorial diseases, such as CAN.
Pediatric Nephrology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Hilary
H
Hotchkiss
Tehua Tearina
TT
Chu
Wayne W
WW
Hancock
Bernd
B
Schröppel
Matthias
M
Kretzler
Holger
H
Schmid
Yeuxun
Y
Liu
Steven
S
Dikman
Enver
E
Akalin
D000328:Adult; D005260:Female; D005355:Fibrosis; D015870:Gene Expression; D020869:Gene Expression Profiling; D006085:Graft Survival / Q000235:genetics*; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous
D006133:Growth Substances