Plumbagin Ameliorates CCl4-Induced Hepatic Fibrosis in Rats via the Epidermal Growth Factor Receptor Signaling Pathway

Epidermal growth factor (EGF) and its signaling molecules, EGFreceptor (EGFR) and signal transducer and activator of transcription factor 3 (STAT3), have been considered to play a role in liver fibrosis and cirrhosis. Plumbagin (PL) is an extracted component from the plant and has been used to treat...

Full description

Bibliographic Details
Main Authors:	Chen, Si, Chen, Yi, Chen, Bi, Cai, Yi-jing, Zou, Zhuo-lin, Wang, Jin-guo, Lin, Zhuo, Wang, Xiao-dong, Fu, Li-yun, Hu, Yao-ren, Chen, Yong-ping, Chen, Da-zhi
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624924/

id	pubmed-4624924
recordtype	oai_dc
spelling	pubmed-46249242015-11-08 Plumbagin Ameliorates CCl4-Induced Hepatic Fibrosis in Rats via the Epidermal Growth Factor Receptor Signaling Pathway Chen, Si Chen, Yi Chen, Bi Cai, Yi-jing Zou, Zhuo-lin Wang, Jin-guo Lin, Zhuo Wang, Xiao-dong Fu, Li-yun Hu, Yao-ren Chen, Yong-ping Chen, Da-zhi Research Article Epidermal growth factor (EGF) and its signaling molecules, EGFreceptor (EGFR) and signal transducer and activator of transcription factor 3 (STAT3), have been considered to play a role in liver fibrosis and cirrhosis. Plumbagin (PL) is an extracted component from the plant and has been used to treat different kinds of cancer. However, its role in regulation of EGFR and STAT3 during liver fibrosis has not been investigated. In this study, the effects of PL on the regulation of EGFR and STAT3 were investigated in carbon tetrachloride (CCl4) induced liver fibrosis and hepatic stellate cells (HSC-T6). PL significantly attenuated liver injury and fibrosis in CCl4 treated rats. At concentrations of 2 to 6 μM, PL did not induce significant cytotoxicity of HSC-T6 cells. Moreover, PL reduced phosphorylation of EGFR and STAT3 in both fibrotic liver and heparin-binding EGF-like growth factor (HB-EGF) treated HSC-T6 cells. Furthermore, PL reduced the expression of α-SMA, EGFR, and STAT3 in both fibrotic liver and HB-EGF treated HSC-T6 cells. In conclusion, plumbagin could ameliorate the development of hepatic fibrosis through its downregulation of EGFR and STAT3 in the liver, especially in hepatic stellate cells. Hindawi Publishing Corporation 2015 2015-10-15 /pmc/articles/PMC4624924/ /pubmed/26550019 http://dx.doi.org/10.1155/2015/645727 Text en Copyright © 2015 Si Chen et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Chen, Si Chen, Yi Chen, Bi Cai, Yi-jing Zou, Zhuo-lin Wang, Jin-guo Lin, Zhuo Wang, Xiao-dong Fu, Li-yun Hu, Yao-ren Chen, Yong-ping Chen, Da-zhi
spellingShingle	Chen, Si Chen, Yi Chen, Bi Cai, Yi-jing Zou, Zhuo-lin Wang, Jin-guo Lin, Zhuo Wang, Xiao-dong Fu, Li-yun Hu, Yao-ren Chen, Yong-ping Chen, Da-zhi Plumbagin Ameliorates CCl4-Induced Hepatic Fibrosis in Rats via the Epidermal Growth Factor Receptor Signaling Pathway
author_facet	Chen, Si Chen, Yi Chen, Bi Cai, Yi-jing Zou, Zhuo-lin Wang, Jin-guo Lin, Zhuo Wang, Xiao-dong Fu, Li-yun Hu, Yao-ren Chen, Yong-ping Chen, Da-zhi
author_sort	Chen, Si
title	Plumbagin Ameliorates CCl4-Induced Hepatic Fibrosis in Rats via the Epidermal Growth Factor Receptor Signaling Pathway
title_short	Plumbagin Ameliorates CCl4-Induced Hepatic Fibrosis in Rats via the Epidermal Growth Factor Receptor Signaling Pathway
title_full	Plumbagin Ameliorates CCl4-Induced Hepatic Fibrosis in Rats via the Epidermal Growth Factor Receptor Signaling Pathway
title_fullStr	Plumbagin Ameliorates CCl4-Induced Hepatic Fibrosis in Rats via the Epidermal Growth Factor Receptor Signaling Pathway
title_full_unstemmed	Plumbagin Ameliorates CCl4-Induced Hepatic Fibrosis in Rats via the Epidermal Growth Factor Receptor Signaling Pathway
title_sort	plumbagin ameliorates ccl4-induced hepatic fibrosis in rats via the epidermal growth factor receptor signaling pathway
description	Epidermal growth factor (EGF) and its signaling molecules, EGFreceptor (EGFR) and signal transducer and activator of transcription factor 3 (STAT3), have been considered to play a role in liver fibrosis and cirrhosis. Plumbagin (PL) is an extracted component from the plant and has been used to treat different kinds of cancer. However, its role in regulation of EGFR and STAT3 during liver fibrosis has not been investigated. In this study, the effects of PL on the regulation of EGFR and STAT3 were investigated in carbon tetrachloride (CCl4) induced liver fibrosis and hepatic stellate cells (HSC-T6). PL significantly attenuated liver injury and fibrosis in CCl4 treated rats. At concentrations of 2 to 6 μM, PL did not induce significant cytotoxicity of HSC-T6 cells. Moreover, PL reduced phosphorylation of EGFR and STAT3 in both fibrotic liver and heparin-binding EGF-like growth factor (HB-EGF) treated HSC-T6 cells. Furthermore, PL reduced the expression of α-SMA, EGFR, and STAT3 in both fibrotic liver and HB-EGF treated HSC-T6 cells. In conclusion, plumbagin could ameliorate the development of hepatic fibrosis through its downregulation of EGFR and STAT3 in the liver, especially in hepatic stellate cells.
publisher	Hindawi Publishing Corporation
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624924/
_version_	1613494452110753792

Plumbagin Ameliorates CCl4-Induced Hepatic Fibrosis in Rats via the Epidermal Growth Factor Receptor Signaling Pathway

Similar Items