Gelatinase B (MMP-9) is not essential in the normal kidney and does not influence progression of renal disease in a mouse model of alport syndrome

Kaya L. Andrews, Tomoko Betsuyaku, Sharon S. Rogers, J. Michael Shipley, Robert M. Senior, Jeffrey H. Miner

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Matrix metalloproteinases are matrix degrading enzymes implicated in many biological processes, including development and inflammation. Gelatinase B (ge1B; also known as MMP-9) is expressed in the kidney and is hypothesized to be involved in basement membrane remodeling and in preventing pathogenic accumulation of extracellular matrix in the kidney. Inhibition of ge1B activity in metanephric organ culture disrupts branching morphogenesis of the ureteric bud, suggesting that ge1B plays a role in kidney development in vivo. We studied kidneys of ge1B-deficient mice to search for developmental, histological, molecular, ultrastructural, and functional defects. Surprisingly, no differences between ge1B-/- and control kidneys were detected, and renal function was normal in ge1B mutants. In addition, ge1B-/- embryonic kidneys developed normally in organ culture. Gelatinase B-deficient mice were bred with Col4a3-/- mice, a model for Alport syndrome, to determine whether ge1B influences the progression of glomerulonephritis. This is an important question, as it has been hypothesized that proteases are involved in damaging Alport glomerular basement membrane. However, the presence or absence of ge1B did not affect the rate of progression of renal disease. Thus, ge1B does not have a discernible role in the normal kidney and ge1B is not involved in the progression of glomerulonephritis in a mouse model of Alport syndrome.

Original languageEnglish
Article number64541
Pages (from-to)303-311
Number of pages9
JournalAmerican Journal of Pathology
Volume157
Issue number1
DOIs
Publication statusPublished - 2000 Jul

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Gelatinase B (MMP-9) is not essential in the normal kidney and does not influence progression of renal disease in a mouse model of alport syndrome'. Together they form a unique fingerprint.

  • Cite this