期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 34, 期 -, 页码 250-258出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2016.03.011
关键词
Dihydroartemisinin; Liver fibrosis; Hepatic stellate cell; Platelet-derived growth factor beta receptor; ERK
资金
- National Natural Science Foundation of China [81270514, 31401210, 31571455]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Youth Natural Science Foundation of Jiangsu Province [BK20140955]
- Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education
- Youth Natural Science Foundation of Nanjing University of Chinese Medicine [13XZR20]
- Natural Science Research General Program of Jiangsu Higher Education Institutions [14KJB310011]
- Open Project Program of National First-Class Key Discipline for Pharmacy of Nanjing University of Chinese Medicine [KYLX-0974]
- Medical Science and technology development Foundation, Nanjing Department of Health [YKK14143]
Liver fibrosis represents a frequent event following chronic insult to trigger wound healing responses in the liver. Activation of hepatic stellate cells (HSCs), which is a pivotal event during liver fibrogenesis, is accompanied by enhanced expressions of a series of marker proteins and pro-fibrogenic signaling molecules. Artemisinin, a powerful antimalarial medicine, is extracted from the Chinese herb Artemisia annua L., and can inhibit the proliferation of cancer cells. Dihydroartemisinin (DHA), the major active metabolite of artemisinin, is able to attenuate lung injury and fibrosis. However, the effect of DHA on liver fibrosis remains unclear. The aim of this study was to investigate the effect of DHA on bile duct ligation-induced injury and fibrosis in rats. DHA improved the liver histological architecture and attenuated collagen deposition in the fibrotic rat liver. Experiments in vitro showed that DHA inhibited the proliferation of HSCs and arrested the cell cycle at the S checkpoint by altering several cell-cycle regulatory proteins. Moreover, DHA reduced the protein expressions of a-SMA alpha 1 (I) collagen and fibronectin, being associated with interference of the platelet-derived growth factor beta receptor (PDGF-beta R)-mediated ERK pathway. These data collectively revealed that DHA relieved liver fibrosis possibly by targeting HSCs via the PDGF-beta R/ERK pathway. DHA may be a therapeutic antifibrotic agent for the treatment of hepatic fibrosis. (C) 2016 Elsevier B.V. All rights reserved.
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