Attenuation of CCl4-Induced Hepatic Fibrosis in Mice by Vaccinating against TGF-beta 1

作者：Fan, Xiaobao; Zhang, Qiannan; Li, Shuang; Lv, Yifei; Su, Houqiang; Jiang, Huiping; Hao, Zhiming^*

来源：PLos One, 2013, 8(12): e82190.

DOI：10.1371/journal.pone.0082190

• GROWTH-FACTOR-BETA
• CELL LUNG-CANCER
• LIVER FIBROSIS
• TNF-ALPHA
• TRANSFORMING GROWTH-FACTOR-BETA-1
• II RECEPTOR
• TGF-BETA
• RAT
• INHIBITION
• THERAPY

Transforming growth factor beta 1 (TGF-beta 1) is the pivotal pro-fibrogenic cytokine in hepatic fibrosis. Reducing the over-produced expression of TGF-beta 1 or blocking its signaling pathways is considered to be a promising therapeutic strategy for hepatic fibrosis. In this study, we evaluated the feasibility of attenuating hepatic fibrosis by vaccination against TGF-beta 1 with TGF-beta 1 kinoids. Two TGF-beta 1 kinoid vaccines were prepared by cross-linking TGF-beta 1-derived polypeptides (TGF-beta 1(25)-[41-65] and TGF-beta 1(30)-[83-112]) to keyhole limpet hemocyanin (KLH). Immunization with the two TGF-beta 1 kinoids efficiently elicited the production of high-levels of TGF-beta 1-specific antibodies against in BALB/c mice as tested by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The antisera neutralized TGF-beta 1-induced growth-inhibition on mink lung epithelial cells (Mv1Lu) and attenuated TGF-beta 1-induced Smad2/3 phosphorylation, alpha-SMA, collagen type 1 alpha 2 (COL1A2), plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression in the rat hepatic stellate cell (HSC) line, HSC-T6. Vaccination against TGF-beta 1 with the kinoids significantly suppressed CCl4-induced collagen deposition and the expression of alpha-SMA and desmin, attenuated hepatocyte apoptosis and accelerated hepatocyte proliferation in BALB/c mice. These results demonstrated that immunization with the TGF-beta 1 kinoids efficiently attenuated CCl4-induced hepatic fibrosis and liver injury. Our study suggests that vaccination against TGF-beta 1 might be developed into a feasible therapeutic approach for the treatment of chronic fibrotic liver diseases.

• 出版日期2013-12-11
• 单位西安交通大学