Critical role of factor XIII in the initial stages of carbon tetrachloride-induced adult liver remodeling.
The transglutaminase-mediated, covalent cross-linking of proteins is an essential step in tissue remodeling after injury. This process provides tissues with extra rigidity and resistance against proteolytic degradation. Plasma coagulation factor XIII (FXIII) is a transglutaminase that promotes cross-linking of the extracellular matrix (ECM) components fibrin and fibronectin to form a provisional matrix in response to tissue damage. However, the functional requirement for this FXIII-mediated cross-linked provisional matrix in adult tissue remodeling remains to be defined. Although it has been proposed that the formation FXIII-mediated fibrin-fibronectin provisional matrix is a critical step for ECM remodeling, we show in an FXIII subunit A-deficient murine model of acute liver injury that the lack of FXIII subunit A did not interfere with collagen reconstruction and resolution after liver injury. Furthermore, FXIIIA deficiency caused significantly increased hepatocyte apoptosis and a delay in hepatocyte regeneration after injury, which were accompanied by a significantly high induction of p53 expression. These findings suggest novel functions of FXIII that the FXIII-mediated covalently cross-linked matrix could promote survival signals for hepatocytes in adult tissue remodeling.
Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Ikuko
I
Tsujimoto
Kei
K
Moriya
Keiko
K
Sakai
Gerhard
G
Dickneite
Takao
T
Sakai
D000818:Animals; D017209:Apoptosis; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002448:Cell Adhesion / Q000502:physiology; D049109:Cell Proliferation; D054338:Cell Transdifferentiation / Q000502:physiology; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology*; D003094:Collagen / Q000502:physiology; D003432:Cross-Linking Reagents / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology; D005176:Factor XIII / Q000502:physiology*; D005177:Factor XIII Deficiency / Q000503:physiopathology*; D026122:Factor XIIIa / Q000502:physiology; D005337:Fibrin / Q000502:physiology; D005340:Fibrinogen / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D055166:Hepatic Stellate Cells / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D014945:Wound Healing / Q000502:physiology
D003432:Cross-Linking Reagents; D005353:Fibronectins; D005337:Fibrin; D005340:Fibrinogen; D003094:Collagen; D005176:Factor XIII; D002251:Carbon Tetrachloride; D026122:Factor XIIIa