Renal allografts with IF/TA display distinct expression profiles of metzincins and related genes

Rödder, S; Scherer, A; Raulf, F; Berthier, C C; Hertig, A; Couzi, L; Durrbach, A; Rondeau, E; Marti, H-P (2009). Renal allografts with IF/TA display distinct expression profiles of metzincins and related genes. American journal of transplantation, 9(3), pp. 517-26. Oxford: Wiley-Blackwell 10.1111/j.1600-6143.2008.02512.x

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Chronic renal allograft injury is often reflected by interstitial fibrosis (IF) and tubular atrophy (TA) without evidence of specific etiology. In most instances, IF/TA remains an irreversible disorder, representing a major cause of long-term allograft loss. As members of the protease family metzincins and functionally related genes are involved in fibrotic and sclerotic processes of the extracellular matrix (ECM), we hypothesized their deregulation in IF/TA. Gene expression and protein level analyses using allograft biopsies with and without Banff'05 classified IF/TA illustrated their deregulation. Expression profiles of these genes differentiated IF/TA from Banff'05 classified Normal biopsies in three independent microarray studies and demonstrated histological progression of IF/TA I to III. Significant upregulation of matrix metalloprotease-7 (MMP-7) and thrombospondin-2 (THBS-2) in IF/TA biopsies and sera was revealed in two independent patient sets. Furthermore, elevated THBS-2, osteopontin (SPP1) and beta-catenin may play regulatory roles on MMP. Our findings further suggest that deregulated ECM remodeling and possibly epithelial to mesenchymal transition (EMT) are implicated in IF/TA of kidney transplants, and that metzincins and related genes play an important role in these processes. Profiling of these genes may be used to complement IF/TA diagnosis and to disclose IF/TA progression in kidney transplant recipients.

Item Type:

Journal Article (Original Article)

Division/Institute:

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

UniBE Contributor:

Marti, Hans-Peter

ISSN:

1600-6135

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:14

Last Modified:

05 Dec 2022 14:22

Publisher DOI:

10.1111/j.1600-6143.2008.02512.x

PubMed ID:

19191772

Web of Science ID:

000263518900010

URI:

https://boris.unibe.ch/id/eprint/32427 (FactScience: 197607)

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