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Author:

Fan, Xiaobao (Fan, Xiaobao.) | Zhang, Qiannan (Zhang, Qiannan.) | Li, Shuang (Li, Shuang.) | Lv, Yifei (Lv, Yifei.) | Su, Houqiang (Su, Houqiang.) | Jiang, Huiping (Jiang, Huiping.) | Hao, Zhiming (Hao, Zhiming.)

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SCIE PubMed Scopus

Abstract:

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.

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Author Community:

  • [ 1 ] [Fan, Xiaobao; Zhang, Qiannan; Li, Shuang; Lv, Yifei; Su, Houqiang; Jiang, Huiping; Hao, Zhiming] Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 1, Dept Gastroenterol, Xian 710049, Peoples R China

Reprint Author's Address:

  • Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 1, Dept Gastroenterol, Xian 710049, Peoples R China.

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Source :

PLOS ONE

ISSN: 1932-6203

Year: 2013

Issue: 12

Volume: 8

3 . 5 3 4

JCR@2013

3 . 2 4 0

JCR@2020

ESI Discipline: MULTIDISCIPLINARY;

ESI HC Threshold:452

JCR Journal Grade:2

CAS Journal Grade:3

Cited Count:

WoS CC Cited Count: 25

SCOPUS Cited Count: 52

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 22

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