Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.

Transforming growth factor β1 (TGF-β1) is the pivotal pro-fibrogenic cytokine in hepatic fibrosis. Reducing the over-produced expression of TGF-β1 or blocking its signaling pathways is considered to be a promising therapeutic strategy for hepatic fibrosis. In this study, we evaluated the feasibility...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xiaobao Fan, Qiannan Zhang, Shuang Li, Yifei Lv, Houqiang Su, Huiping Jiang, Zhiming Hao
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/007d329ef4d04654b1b3b8085e3a0f1c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:007d329ef4d04654b1b3b8085e3a0f1c
record_format	dspace
spelling	oai:doaj.org-article:007d329ef4d04654b1b3b8085e3a0f1c2021-11-18T08:42:26ZAttenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.1932-620310.1371/journal.pone.0082190https://doaj.org/article/007d329ef4d04654b1b3b8085e3a0f1c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349218/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Transforming growth factor β1 (TGF-β1) is the pivotal pro-fibrogenic cytokine in hepatic fibrosis. Reducing the over-produced expression of TGF-β1 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-β1 with TGF-β1 kinoids. Two TGF-β1 kinoid vaccines were prepared by cross-linking TGF-β1-derived polypeptides (TGF-β1(25)-[41-65] and TGF-β1(30)-[83-112]) to keyhole limpet hemocyanin (KLH). Immunization with the two TGF-β1 kinoids efficiently elicited the production of high-levels of TGF-β1-specific antibodies against in BALB/c mice as tested by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The antisera neutralized TGF-β1-induced growth-inhibition on mink lung epithelial cells (Mv1Lu) and attenuated TGF-β1-induced Smad2/3 phosphorylation, α-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-β1 with the kinoids significantly suppressed CCl4-induced collagen deposition and the expression of α-SMA and desmin, attenuated hepatocyte apoptosis and accelerated hepatocyte proliferation in BALB/c mice. These results demonstrated that immunization with the TGF-β1 kinoids efficiently attenuated CCl4-induced hepatic fibrosis and liver injury. Our study suggests that vaccination against TGF-β1 might be developed into a feasible therapeutic approach for the treatment of chronic fibrotic liver diseases.Xiaobao FanQiannan ZhangShuang LiYifei LvHouqiang SuHuiping JiangZhiming HaoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e82190 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaobao Fan Qiannan Zhang Shuang Li Yifei Lv Houqiang Su Huiping Jiang Zhiming Hao Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.
description	Transforming growth factor β1 (TGF-β1) is the pivotal pro-fibrogenic cytokine in hepatic fibrosis. Reducing the over-produced expression of TGF-β1 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-β1 with TGF-β1 kinoids. Two TGF-β1 kinoid vaccines were prepared by cross-linking TGF-β1-derived polypeptides (TGF-β1(25)-[41-65] and TGF-β1(30)-[83-112]) to keyhole limpet hemocyanin (KLH). Immunization with the two TGF-β1 kinoids efficiently elicited the production of high-levels of TGF-β1-specific antibodies against in BALB/c mice as tested by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The antisera neutralized TGF-β1-induced growth-inhibition on mink lung epithelial cells (Mv1Lu) and attenuated TGF-β1-induced Smad2/3 phosphorylation, α-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-β1 with the kinoids significantly suppressed CCl4-induced collagen deposition and the expression of α-SMA and desmin, attenuated hepatocyte apoptosis and accelerated hepatocyte proliferation in BALB/c mice. These results demonstrated that immunization with the TGF-β1 kinoids efficiently attenuated CCl4-induced hepatic fibrosis and liver injury. Our study suggests that vaccination against TGF-β1 might be developed into a feasible therapeutic approach for the treatment of chronic fibrotic liver diseases.
format	article
author	Xiaobao Fan Qiannan Zhang Shuang Li Yifei Lv Houqiang Su Huiping Jiang Zhiming Hao
author_facet	Xiaobao Fan Qiannan Zhang Shuang Li Yifei Lv Houqiang Su Huiping Jiang Zhiming Hao
author_sort	Xiaobao Fan
title	Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.
title_short	Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.
title_full	Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.
title_fullStr	Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.
title_full_unstemmed	Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.
title_sort	attenuation of ccl4-induced hepatic fibrosis in mice by vaccinating against tgf-β1.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/007d329ef4d04654b1b3b8085e3a0f1c
work_keys_str_mv	AT xiaobaofan attenuationofccl4inducedhepaticfibrosisinmicebyvaccinatingagainsttgfb1 AT qiannanzhang attenuationofccl4inducedhepaticfibrosisinmicebyvaccinatingagainsttgfb1 AT shuangli attenuationofccl4inducedhepaticfibrosisinmicebyvaccinatingagainsttgfb1 AT yifeilv attenuationofccl4inducedhepaticfibrosisinmicebyvaccinatingagainsttgfb1 AT houqiangsu attenuationofccl4inducedhepaticfibrosisinmicebyvaccinatingagainsttgfb1 AT huipingjiang attenuationofccl4inducedhepaticfibrosisinmicebyvaccinatingagainsttgfb1 AT zhiminghao attenuationofccl4inducedhepaticfibrosisinmicebyvaccinatingagainsttgfb1
_version_	1718421422111457280

Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.

Ejemplares similares