Protective role of thrombin activatable fibrinolysis inhibitor in obstructive nephropathy-associated tubulointerstitial fibrosis.
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.
Bruno
N E
NE
Department of Diabetes and Endocrinology, Mie University Graduate School of Medicine, Tsu-city, Mie, Japan.
Yano
Y
Y
Takei
Y
Y
Gabazza
E C
EC
Qin
L
L
Nagashima
M
M
Morser
J
J
D'Alessandro-Gabazza
C N
CN
Taguchi
O
O
Sumida
Y
Y
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*
D016207:Cytokines; D025901:Carboxypeptidase B2; D005341:Fibrinolysin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D006909:Hydroxyproline