Involvement of the Transforming Growth Factor β in the Pathogenesis of Hereditary Hemorrhagic Telangiectasia

E.      Jirillo; L.      Amati; P.      Suppressa; D.      Cirimele; E.      Guastamacchia; V.      Covelli; E.      Tafaro; C.      Sabba

Abstract

Hereditary hemorrhagic telangiectasia (HHT) is characterized by vessel alterations such as dilatation of postcapillary venules and arterio-venous communications, which account for the major clinical manifestations of the disease. Two types of HHT have been characterized HHT-1 and HHT-2, respectively, depending the former on endoglin mutations and the latter on activin receptor-like kinase 1 (ALK-1) mutations. Both endoglin and ALK-1 bind to the transforming growth factor (TGF) superfamily which, physiologically, regulates the activities of endothelial cells and also those related to the extracellular matrix. In this review, the salient features of TGF-β will be outlined with special reference to its activity on the immune system and on tumorigenesis. Furthermore, the involvement of TGF-β in the pathogenesis of some gastrointestinal diseases will be discussed and, in particular, in the course of liver disease, Helicobacter pylori infection and inflammatory bowel disease. In the light of these data and of animal model of HHT, the potential risk of developing other diseases in HHT patients will be discussed.

Keywords: Activin receptor-like kinase 1, angiogenesis, endoglin, hereditary hemorrhagic telangiectasia, immunity, transforming, growth factor, tumorigenesis