MMP-2 inhibition reduces renal macrophage infiltration with increased fibrosis in UUO.
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.
Nishida
Masashi
M
Department of Pediatric Cardiology and Nephrology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan. mnishida@koto.kpu-m.ac.jp
Okumura
Yasuko
Y
Ozawa
Sei-Ichiro
S
Shiraishi
Isao
I
Itoi
Toshiyuki
T
Hamaoka
Kenji
K
D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D013876:Thiophenes / Q000008:administration & dosage*; D014517:Ureteral Obstruction / Q000201:enzymology* / Q000473:pathology*
C500127:(2R)-2-(5-(4-(ethylmethylamino)phenyl)thiophene-2-sulfonylamino)-3-methylbutyric acid; D061965:Matrix Metalloproteinase Inhibitors; D013876:Thiophenes