Regulation of proteolysis on epithelial cell membrane and its implication in the epithelial disorders

细胞外蛋白水解在多细胞生物的体内平衡和疾病进展中起着关键作用。我们分析了表达在上皮细胞表面的膜结合丝氨酸蛋白酶抑制剂-肝细胞生长因子激活因子抑制剂1型（HAI-1）及其靶蛋白酶（HGF激活因子、基质酶等）在细胞周围生物活性分子加工、上皮完整性、癌变和癌症进展中的作用。我们的数据揭示了HAI-1在正常调节的表皮角质细胞角化、毛发角质层形成和肠上皮完整性中的关键作用。我们还发现HAI-1可能是上皮癌变和肿瘤侵袭的重要抑制因子。

Pericellular proteolysis has critical roles in homeostasis and disease progression in multicellular organisms. We analyzed roles for hepatocyte growth factor activator inhibitor type 1(HAI-1), a membrane-bound serine protease inhibitor expressed on the epithelial cell surface, and its target proteases(HGF activator, matriptase, etc) in processing of pericellular bioactive molecules, epithelial integrity, carcinogenesis and cancer progression. Our data uncovered critical roles of HAI-1 in normal regulated keratinization of epidermal keratinocytes, formation of hair cuticle and intestinal epithelial integrity. We also found that HAI-1 may be an important suppressor of epithelial carcinogenesis and cancer invasion.