Literature DB >> 17210124

MMP-2 inhibition reduces renal macrophage infiltration with increased fibrosis in UUO.

Masashi Nishida1, Yasuko Okumura, Sei-Ichiro Ozawa, Isao Shiraishi, Toshiyuki Itoi, Kenji Hamaoka.   

Abstract

We examined the role of matrix metalloproteinase-2 (MMP-2) in renal fibrosis and its effect on interstitial macrophage infiltration in a mouse model of unilateral ureteral obstruction (UUO). TISAM, a selective inhibitor of MMP-2, was administered during early stage (day -2 to 4; protocol A) and late stage (day 7 to 13; protocol B) after UUO. Treatment with TISAM accelerated fibrosis both at day 5 (A) and at day 14 (B). The degree of macrophage infiltration was decreased by the treatment with TISAM at day 14, but not at day 5. In vitro macrophage migration assay showed a greater migration to renal tissue of control UUO kidney (day 14) than to TISAM-treated kidney, which was suppressed by preincubating macrophages with RGDS, a fibronectin degradation peptide. These results suggest that MMP-2 acts to accelerate macrophage infiltration in the late stage of UUO, possibly by degrading extracellular matrix components.

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Year:  2006        PMID: 17210124     DOI: 10.1016/j.bbrc.2006.12.165

Source DB:  PubMed          Journal:  Biochem Biophys Res Commun        ISSN: 0006-291X            Impact factor:   3.575


  21 in total

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