title: Role of matrix metalloproteinase-2 in recovery after tubular damage in acute kidney injury in mice.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMPs) are zinc endopeptidases that degrade extracellular matrix and are involved in the pathogenesis of ischemic damage in acute kidney injury (AKI). In the present study, we analyzed the role of MMP-2 in the repair process in ischemic AKI.
  
  
  METHODS
  AKI was induced in MMP-2 wild-type (MMP-2(+/+)) and MMP-2-deficient (MMP-2(-/-)) mice by 90-min renal artery clamping followed by reperfusion. Renal histology and the activity and distribution of MMP-2 were examined from day 1 to day 14. During the recovery from AKI, MMP-2(+/+) mice were also treated with MMP-2/MMP-9 inhibitor.
  
  
  RESULTS
  In both MMP-2(+/+) and MMP-2(-/-) mice, AKI developed on day 1 after ischemia/reperfusion with widespread acute tubular injury, but subsequent epithelial cell proliferation was evident on days 3-7. During the repair process, active MMP-2 and MMP-9 increased in regenerating tubular epithelial cells in MMP-2(+/+) mice on days 7-14, and the tubular repair process was almost complete by day 14. On the other hand, in MMP-2(-/-) mice, less prominent proliferation of tubular epithelial cells was evident on days 3 and 7, and damaged tubules that were covered with elongated and immature regenerated epithelial cells were identified on days 7 and 14. Incomplete recovery of injured microvasculature was also noted with persistent macrophage infiltration. Similarly, treatment with MMP-2/MMP-9 inhibitor resulted in impaired recovery in MMP-2(+/+) mice.
  
  
  CONCLUSIONS
  MMP-2 is involved in tubular repair after AKI. The use of the MMP-2/MMP-9 inhibitor was a disadvantage when it was administered during the repair stage of ischemic AKI. Treatment with MMP inhibitor for AKI needs to be modified to enhance recovery from AKI.
authors.affiliation: Division of Neurology, Nephrology and Rheumatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kaneko
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Akiko
authors.initials: A
authors.lastname: Mii
authors.forename: Emiko
authors.initials: E
authors.lastname: Fujita
authors.forename: Teppei
authors.initials: T
authors.lastname: Fujino
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kunugi
authors.forename: Xuanyi
authors.initials: X
authors.lastname: Du
authors.forename: Toshio
authors.initials: T
authors.lastname: Akimoto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tsuruoka
authors.forename: Ryuji
authors.initials: R
authors.lastname: Ohashi
authors.forename: Yukinari
authors.initials: Y
authors.lastname: Masuda
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iino
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Katayama
authors.forename: Yuh
authors.initials: Y
authors.lastname: Fukuda
mesh_terms: D058186:Acute Kidney Injury / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D004847:Epithelial Cells / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse