Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Am J Pathol. 2011 Dec;179(6):3011-9. doi: 10.1016/j.ajpath.2011.08.037. Epub 2011 Oct 19.
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.
转谷氨酰胺酶介导的蛋白质共价交联是损伤后组织重塑的一个重要步骤。这个过程为组织提供了额外的刚性和抵抗蛋白水解降解的能力。血浆凝血因子 XIII (FXIII) 是一种转谷氨酰胺酶，它能促进细胞外基质 (ECM) 成分纤维蛋白和纤维连接蛋白的交联，以响应组织损伤形成临时基质。然而，FXIII 介导的交联临时基质在成人组织重塑中的功能需求仍有待确定。尽管有人提出 FXIII 介导的纤维蛋白-纤维连接蛋白临时基质的形成是 ECM 重塑的关键步骤，但我们在急性肝损伤的 FXIII 亚单位 A 缺陷型小鼠模型中表明，缺乏 FXIII 亚单位 A 并不干扰肝损伤后胶原的重建和降解。此外，FXIIIA 缺乏导致损伤后肝细胞凋亡显著增加和肝细胞再生延迟，同时伴随着 p53 表达的显著上调。这些发现提示 FXIII 具有新的功能，即 FXIII 介导的共价交联基质可以促进成年组织重塑中肝细胞的存活信号。
