Sasaki Motoko, Tsuneyama Koichi, Saito Takahito, Kataoka Hiroaki, Mollenhauer Jan, Poustka Annemarie, Nakanuma Yasuni
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Liver Int. 2004 Feb;24(1):29-37. doi: 10.1111/j.1478-3231.2004.00883.x.
BACKGROUND/AIM: Trefoil factor family (TFF)1,2,3 are involved in a homeostasis/repair process of mucosal epithelia. In this study, the significance of TFF family and deleted in the malignant brain tumor-1 (DMBT1), a putative receptor of TFF2, in the intrahepatic biliary tree was investigated in normal and diseased livers.
Expression of TFF1,2,3 and DMBT1 were examined immunohistochemically in primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), chronic viral hepatitis (CVH), extrahepatic biliary obstruction (EBO), and normal livers.
In normal livers, TFF1,3 and DMBT1 were infrequently detectable in large and rarely in small bile ducts, respectively. TFF2 was not detectable in large bile ducts. In large bile duct diseases (PSC and EBO), expression of TFF3 and DMBT1 were increased. In small bile duct diseases (PBC and CVH), expression of TFF2/DMBT1 was induced in moderately to severely damaged ducts irrespective of etiology.
The intrahepatic biliary tree shows a site-characteristic expression and induction of TFF1,2,3 and DMBT1. In large bile ducts, TFF1,3 were constitutively expressed and increased in pathologic bile ducts. In small bile ducts, TFF2/DMBT1 is induced in damaged ducts irrespective of etiologies. However, the cytoprotective/repair property of TFF2/DMBT1 may not be enough to prevent the following bile duct loss in PBC.
背景/目的:三叶因子家族(TFF)1、2、3参与黏膜上皮的稳态/修复过程。在本研究中,我们在正常和患病肝脏中研究了TFF家族以及恶性脑肿瘤缺失-1(DMBT1,一种推测的TFF2受体)在肝内胆管树中的意义。
采用免疫组织化学方法检测原发性胆汁性肝硬化(PBC)、原发性硬化性胆管炎(PSC)、慢性病毒性肝炎(CVH)、肝外胆管梗阻(EBO)及正常肝脏中TFF1、2、3和DMBT1的表达。
在正常肝脏中,TFF1、3和DMBT1分别在大胆管中很少能检测到,在小胆管中则极少能检测到。TFF2在大胆管中无法检测到。在大胆管疾病(PSC和EBO)中,TFF3和DMBT1的表达增加。在小胆管疾病(PBC和CVH)中,无论病因如何,TFF2/DMBT1在中度至重度受损的胆管中被诱导表达。
肝内胆管树呈现出TFF1、2、3和DMBT1的位点特征性表达和诱导。在大胆管中,TFF1、3组成性表达且在病理性胆管中增加。在小胆管中,无论病因如何,TFF2/DMBT1在受损胆管中被诱导表达。然而,TFF2/DMBT1的细胞保护/修复特性可能不足以防止PBC中随后的胆管丢失。