Impaired healing of cutaneous wounds and colonic anastomoses in mice lacking thrombin-activatable fibrinolysis inhibitor.
Plasmin and other components of the plasminogen activation system play an important role in tissue repair by regulating extracellular matrix remodeling, including fibrin degradation. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase that, after activation, can attenuate plasmin-mediated fibrin degradation by removing the C-terminal lysine residues from fibrin, which play a role in the binding and activation of plasminogen. To test the hypothesis that TAFI is an important determinant in the control of tissue repair, we investigated the effect of TAFI deficiency on the healing of cutaneous wounds and colonic anastomoses. Histological examination revealed inappropriate organization of skin wound closure in the TAFI knockout mice, including an altered pattern of epithelial migration. The time required to completely heal the cutaneous wounds was slightly delayed in TAFI-deficient mice. Healing of colonic anastomoses was also impaired, as reflected by decreased strength of the tissue at the site of the suture, and by bleeding complications in 3 of 14 animals. Together, these abnormalities resulted in increased mortality in TAFI-deficient mice after colonic anastomoses. Although our study shows that tissue repair, including re-epithelialization and scar formation, occurs in TAFI-deficient mice, TAFI appears to be important for appropriate organization of the healing process.
te Velde
E A
EA
Department of Medical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands.
Wagenaar
G T M
GT
Reijerkerk
A
A
Roose-Girma
M
M
Borel Rinkes
I H M
IH
Voest
E E
EE
Bouma
B N
BN
Gebbink
M F B G
MF
Meijers
J C M
JC
D000714:Anastomosis, Surgical; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D043424:Carboxypeptidase B / Q000235:genetics; D025901:Carboxypeptidase B2 / Q000235:genetics* / Q000378:metabolism*; D002268:Carboxypeptidases / Q000737:chemistry; D002465:Cell Movement; D003106:Colon / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D004622:Embryo, Mammalian / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology; D005341:Fibrinolysin / Q000378:metabolism; D005822:Genetic Vectors; D015603:Keratinocytes / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D010958:Plasminogen / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013997:Time Factors; D014945:Wound Healing
D010958:Plasminogen; D004247:DNA; D002268:Carboxypeptidases; D043424:Carboxypeptidase B; D025901:Carboxypeptidase B2; D005341:Fibrinolysin