title: Oral administration of recombinant adeno-associated virus-mediated bone morphogenetic protein-7 suppresses CCl(4)-induced hepatic fibrosis in mice.
abstract: Fibrogenesis and hepatocyte degeneration are the main pathological processes in chronic liver diseases. Transforming growth factor-β1 (TGF-β1) is the key profibrotic cytokine in hepatic fibrosis. Bone morphogenetic protein-7 (BMP-7) is a potent antagonist of TGF-β1 and an antifibrotic factor. In this study, we generated a recombinant adeno-associated virus carrying BMP-7 (AAV-BMP-7) and tested its ability to suppress carbon tetrachloride (CCl(4))-induced hepatic fibrosis when orally administered to mice. Our results show that the ectopic expression of BMP-7 in gastrointestinal (GI) mucosa due to the AAV-BMP-7 administration led to the long-term elevation of serum BMP-7 concentrations and resulted in the drastic amelioration of CCl(4)-induced hepatic fibrosis in BALB/c mice. Immunostaining for α-smooth muscle actin (α-SMA) and desmin demonstrated that AAV-BMP-7 inhibited the activation of hepatic stellate cells (HSCs) in the fibrotic mouse liver. Moreover, the ectopic expression of BMP-7 promoted hepatocyte proliferation, as confirmed by an increase in the amount of proliferating cell nuclear antigen (PCNA)-positive hepatocytes in the mice that received AAV-BMP-7. Our results clearly indicate that BMP-7 is capable of inhibiting hepatic fibrosis and promoting hepatocyte regeneration. We suggest that oral AAV-BMP-7 could be developed into a safe, simple, and effective therapy for hepatic fibrosis.
authors: Department of Gastroenterology, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. haozhm@yahoo.com.cn
authors: Zhi-Ming
authors: ZM
authors: Hao
authors: Min
authors: M
authors: Cai
authors: Yi-Fei
authors: YF
authors: Lv
authors: Yan-Hua
authors: YH
authors: Huang
authors: Hong-Hong
authors: HH
authors: Li
mesh_terms: D000199:Actins / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D049109:Cell Proliferation; D054407:Chemokine CCL4; D000229:Dependovirus / Q000235:genetics*; D003893:Desmin / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000502:physiology; D006820:Hyaluronic Acid / Q000097:blood; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics
chemical_list: D000199:Actins; D055419:Bone Morphogenetic Protein 7; D054407:Chemokine CCL4; D003893:Desmin; D011994:Recombinant Proteins; C525820:bmp7 protein, mouse; D006820:Hyaluronic Acid; D006909:Hydroxyproline