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Angiotensin II induces connective tissue growth factor expression in human hepatic stellate cells by a transforming growth factor beta-independent mechanism
Li, Ao1,2; Zhang, Jingyao1; Zhang, Xiaoxun1; Wang, Jun1; Wang, Songsong2; Xiao, Xiao1; Wang, Rui1; Li, Peng2; Wang, Yitao2
2017-08-10
Source PublicationSCIENTIFIC REPORTS
ISSN2045-2322
Volume7
Abstract

Angiotensin II (Ang II) promotes hepatic fibrosis by increasing extracellular matrix (ECM) synthesis. Connective tissue growth factor (CTGF) plays a crucial role in the pathogenesis of hepatic fibrosis and emerges as downstream of the profibrogenic cytokine transforming growth factor-beta (TGF-beta). We aimed to investigate the molecular events that lead from the Ang II receptor to CTGF upregulation in human hepatic stellate cells, a principal fibrogenic cell type. Ang II produced an early, AT1 receptor-dependent stimulation of CTGF expression and induced a rapid activation of PKC and its downstream p38 MAPK, thereby activating a nuclear factor-kappa B (NF-kappa B) and Smad2/3 cross-talk pathway. Chemical blockade of NF-kappa B and Smad2/3 signaling synergistically diminished Ang II-mediated CTGF induction and exhibited an additive effect in abrogating the ECM accumulation caused by Ang II. Furthermore, we demonstrated that CTGF expression was essential for Ang II-mediated ECM synthesis. Interestingly, the ability of dephosphorylated, but not phosphorylated JNK to activate Smad2/3 signaling revealed a novel role of JNK in Ang II-mediated CTGF overexpression. These results suggest that Ang II induces CTGF expression and ECM accumulation through a special TGF-beta-independent interaction between the NF-kappa B and Smad2/3 signals elicited by the AT1/PKC alpha/p38 MAPK pathway.

DOIhttp://doi.org/10.1038/s41598-017-08334-x
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000407400500073
PublisherNATURE PUBLISHING GROUP
The Source to ArticleWOS
Fulltext Access
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, 999078, China
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Li, Ao,Zhang, Jingyao,Zhang, Xiaoxun,et al. Angiotensin II induces connective tissue growth factor expression in human hepatic stellate cells by a transforming growth factor beta-independent mechanism[J]. SCIENTIFIC REPORTS,2017,7.
APA Li, Ao.,Zhang, Jingyao.,Zhang, Xiaoxun.,Wang, Jun.,Wang, Songsong.,...&Wang, Yitao.(2017).Angiotensin II induces connective tissue growth factor expression in human hepatic stellate cells by a transforming growth factor beta-independent mechanism.SCIENTIFIC REPORTS,7.
MLA Li, Ao,et al."Angiotensin II induces connective tissue growth factor expression in human hepatic stellate cells by a transforming growth factor beta-independent mechanism".SCIENTIFIC REPORTS 7(2017).
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