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Ex vivo real‐time MMP activation in kidney in hyperhomocysteinemia
Author(s) -
Sen Utpal,
Metreveli Naira,
Vacek Thomas,
Hughes William M,
Tyagi Suresh C
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.942.10
Subject(s) - kidney , kidney disease , hyperhomocysteinemia , medicine , matrix metalloproteinase , homocysteine , endocrinology , ex vivo , polycystic kidney disease , in vivo , biology , microbiology and biotechnology
Polycystic kidney disease is the primary cause of renal pathology. Very recent studies have demonstrated a positive correlation between plasma homocysteine (Hcy) levels and development of chronic kidney disease; however, the mechanism of glomerular matrix remodeling in Hcy‐induced renal failure is unclear. Here, we hypothesize that hyperhomocysteinemia (HHcy) induces the activation of matrix metalloproteinases (MMPs) in the kidney, which causes acute renal failure. Therefore, we sought to determine the effect of HHcy on MMP activation in isolated perfused kidney. The kidneys from wild type (C57BL/6J) mice were isolated and perfused with physiological salt solution (PSS) for various time frames containing fluorogenic MMP‐2 and ‐9 substrates in presence or absence of Hcy (200 μM). PSS perfused kidney served as control. After perfusion, fluorescence was measured by KODAK 4000 MM imaging station. The kidney perfused with MMP‐2 and ‐9 substrates for 3 hr, in conjunction with Hcy, showed robust increases in MMP activation. This was measured by increases in fluorescence compared to either substrate or PSS alone. The results from acute and real‐time imaging show that HHcy causes MMP‐2 and ‐9 activation in the kidney, and this activation is related to renovascular remodeling during kidney failure.