Meta-analyses qualify metzincins and related genes as acute rejection markers in renal transplant patients

Rödder, S; Scherer, A; Körner, M; Eisenberger, U; Hertig, A; Raulf, F; Rondeau, E; Marti, H-P (2010). Meta-analyses qualify metzincins and related genes as acute rejection markers in renal transplant patients. American journal of transplantation, 10(2), pp. 286-97. Oxford: Wiley-Blackwell 10.1111/j.1600-6143.2009.02928.x

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Definition of acute renal allograft rejection (AR) markers remains clinically relevant. Features of T-cell-mediated AR are tubulointerstitial and vascular inflammation associated with excessive extracellular matrix (ECM) remodeling, regulated by metzincins, including matrix metalloproteases (MMP). Our study focused on expression of metzincins (METS), and metzincins and related genes (MARGS) in renal allograft biopsies using four independent microarray data sets. Our own cases included normal histology (N, n = 20), borderline changes (BL, n = 4), AR (n = 10) and AR + IF/TA (n = 7). MARGS enriched in all data sets were further examined on mRNA and/or protein level in additional patients. METS and MARGS differentiated AR from BL, AR + IF/TA and N in a principal component analysis. Their expression changes correlated to Banff t- and i-scores. Two AR classifiers, based on METS (including MMP7, TIMP1), or on MARGS were established in our own and validated in the three additional data sets. Thirteen MARGS were significantly enriched in AR patients of all data sets comprising MMP7, -9, TIMP1, -2, thrombospondin2 (THBS2) and fibrillin1. RT-PCR using microdissected glomeruli/tubuli confirmed MMP7, -9 and THBS2 microarray results; immunohistochemistry showed augmentation of MMP2, -9 and TIMP1 in AR. TIMP1 and THBS2 were enriched in AR patient serum. Therefore, differentially expressed METS and MARGS especially TIMP1, MMP7/-9 represent potential molecular AR markers.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Körner Jachertz, Meike; Eisenberger, Ute and Marti, Hans-Peter

ISSN:

1600-6135

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:08

Last Modified:

04 May 2014 23:04

Publisher DOI:

10.1111/j.1600-6143.2009.02928.x

PubMed ID:

19958327

Web of Science ID:

000273884800017

URI:

https://boris.unibe.ch/id/eprint/702 (FactScience: 200418)

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