Fibroblast activation protein and chronic liver disease
Fibroblast activation protein and chronic liver disease
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DOI：
10.2741/2918
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发表时间：
2008-01-01
影响因子：
3.1
通讯作者：
Gorrell, Mark D.
中科院分区：
文献类型：
--
作者：
Wang, Xin Maggie;Yao, Tsun-Wen;Gorrell, Mark D.
成纤维细胞活化蛋白（FAP）是二肽基肽酶IV（DPIV）基因家族的成员，与DPIV基因最为相似。该家族的四个成员DPIV、FAP、DP 8和DP 9具有罕见的催化活性，水解距离底物N末端两个残基的脯氨酰键。晶体结构显示FAP的可溶形式包含两个结构域，α/β-水解酶结构域和8-叶片β-螺旋桨结构域。这两个结构域之间的界面形成催化口袋，和底物进入内部活性位点的开口。FAP同二聚体在结构上与DPIV非常相似，但FAP糖蛋白表达主要限于患病和受损组织中的间充质细胞，特别是慢性损伤肝脏中的组织重塑区域。FAP肽底物包括变性胶原和α 2-抗纤溶酶。FAP在肿瘤和纤维化组织中的功能作用尚未完全了解。本文综述了FAP在慢性肝损伤发病机制中的作用。
Fibroblast activation protein (FAP) is the member of Dipeptidyl Peptidase IV (DPIV) gene family that is most similar to DPIV. Four members of this family, DPIV, FAP, DP8 and DP9 possess a rare catalytic activity, hydrolysis of a prolyl bond two residues from the substrate N terminus. Crystal structures show that the soluble form of FAP comprises two domains, an alpha/beta-hydrolase domain and an 8-blade beta-propeller domain. The interface between these two domains forms the catalytic pocket, and an opening for substrate access to the internal active site. The FAP homodimer is structurally very similar to DPIV but FAP glycoprotein expression is largely confined to mesenchymal cells in diseased and damaged tissue, notably the tissue remodelling region in chronically injured liver. FAP peptide substrates include denatured collagen and alpha2-antiplasmin. The functional roles of FAP in tumors and fibrotic tissue are not fully understood. This review places FAP in the context of chronic liver injury pathogenesis.