The Expression of Bone Morphogenetic Protein-7 in Rat Liver Injury

• Main Authors: Ruei-Chen Hung, 洪瑞辰
• Other Authors: Chao-Tien Hsu
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/34897439452531323000

碩士 === 中國醫藥大學 === 醫學檢驗生物技術學系碩士班 === 96 === Background & Aim : Bone morphogenetic proteins (BMPs) play an important role in cell differentiation, regeneration and repair of tissue damage. The recent findings of bone morphogenetiic protein-7 can inhibit TGF-β induced fibrosis via smad signal pathway, and this anti-fibrosis mechanism is called mesenchymal-epithelial transition (MET).We investigated the expression of BMP-7 in bile duct obstruction induced liver fibrosis. Method : Male Sprague-Dawley rats were randomized to four group (n= 6 in each group). Rats submitted to common bile duct ligation for 3 days, 2 weeks and 4 weeks were compared with those from controls, which underwent laparotomy but not bile duct ligation. We used the hematoxyline & eosin stain, immunohistochemistry stain, indirect double immunofluorescence stain, westurn blotting, and reverse-transcription PCR to observe the expression of BMP-7 in bile duct obstruction induced liver injury. Result : Our study shows bile duct proliferation and liver cell damage, inflammation are marked in BDL groups, BDL 4 weeks > 2 weeks >3 days. GOT, GPT, abnormal plasma alanine transaminase (ALT) and total bilirubin levels were noted in BDL rats. The mRNA and protein of BMP-7 are increased in all BDL groups comparison with control. BMP-7 mostly localizes to hepatocytes in control group. In BDL groups, the BMP-7 localizes to nonparenchymal cells (Kupffer cell, fibroblast, myoepithelial cells, and inflammatory cells) and a few hepatocytes around the bile ducts. The BMP receptor II localizes to nonparenchymal cells (Kupffer cells, fibroblast, myoepithelial cells, epithelial cells,and endothelial cells) around the bile ducts in BDL group. In indirect double immunofluorescence stain, BMP-7 and BMPR II localizes to fibroblast and myoepithelial cells. Discussion : Our study showed there are more expression of BMP-7 in nonparenchymal cell (fibroblast, myoepithelial cells, and inflammatory cells) than liver cells, and BMP receptor II also express in nonparenchymal cell (fibroblast, myoepithelial cells, and inflammatory cells) in bile duct ligation induced liver damage. This finding showed that BMP-7 may be associated with anti-inflammation and anti-liver fibrosis in BDL induced liver injury. Key word : common bile duct ligation (CBDL, BDL) , bone morphogenetic protein (BMP) , transforming growth factor-β(TGF-β) , mesenchymal-epithelial transition (MET), epithelial-mesenchymal transition (EMT)