title: Protective role of thrombin activatable fibrinolysis inhibitor in obstructive nephropathy-associated tubulointerstitial fibrosis.
abstract: BACKGROUND
  Thrombin-activatable fibrinolysis inhibitor (TAFI) has been reported to affect wound healing and fibrotic processes, but its role in renal tubulointerstitial fibrosis remains unknown.
  
  
  OBJECTIVE
  To study its potential role, we compared TAFI-deficient and wild-type mice for the degree of renal fibrosis caused by unilateral ureteral obstruction (UUO).
  
  
  METHODS
  The grade of tubulointerstitial fibrosis, the activity of plasmin, MMP-2 and MMP-9 were evaluated on days 4 and 9 after UUO.
  
  
  RESULTS
  The renal content of hydroxyproline and the activity of plasmin, MMP-2 and MMP-9 were significantly increased in kidneys with UUO from TAFI-deficient mice compared with those from wild-type mice. These differences disappeared when animals with UUO from both groups were treated with the plasmin inhibitor tranexamic acid. The renal concentrations of fibrogenic cytokines were also significantly elevated in kidneys with UUO from TAFI-deficient mice compared with those from wild-type mice.
  
  
  CONCLUSIONS
  The results of this study suggest that increased renal activity of plasmin in TAFI-deficient mice causes increased renal interstitial fibrosis in obstructive nephropathy.
authors.affiliation: Department of Diabetes and Endocrinology, Mie University Graduate School of Medicine, Tsu-city, Mie, Japan.
authors.forename: N E
authors.initials: NE
authors.lastname: Bruno
authors.forename: Y
authors.initials: Y
authors.lastname: Yano
authors.forename: Y
authors.initials: Y
authors.lastname: Takei
authors.forename: E C
authors.initials: EC
authors.lastname: Gabazza
authors.forename: L
authors.initials: L
authors.lastname: Qin
authors.forename: M
authors.initials: M
authors.lastname: Nagashima
authors.forename: J
authors.initials: J
authors.lastname: Morser
authors.forename: C N
authors.initials: CN
authors.lastname: D'Alessandro-Gabazza
authors.forename: O
authors.initials: O
authors.lastname: Taguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Sumida
mesh_terms: D000818:Animals; D025901:Carboxypeptidase B2 / Q000172:deficiency / Q000502:physiology*; D016207:Cytokines / Q000032:analysis; D005341:Fibrinolysin / Q000032:analysis*; D005355:Fibrosis / Q000209:etiology*; D006909:Hydroxyproline / Q000032:analysis; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D014517:Ureteral Obstruction / Q000150:complications*
chemical_list: D016207:Cytokines; D025901:Carboxypeptidase B2; D005341:Fibrinolysin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D006909:Hydroxyproline