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15d-Deoxy-Delta12,14-prostaglandin J2 modulates collagen type I synthesis in human hepatic stellate cells by inducing oxidative stress

Cited 6 time in Web of Science Cited 6 time in Scopus
Authors
Kim, Kyung-Ah; Lim, Young-Suk; Kim, Kang-Mo; Yoon, Jung-Hwan; Lee, Hyo-Suk
Issue Date
2005-08-16
Publisher
Elsevier
Citation
Prostaglandins Leukot Essent Fatty Acids. 2005 Nov;73(5):361-7.
Keywords
Antioxidants/pharmacologyApoptosis/*drug effectsCell Survival/drug effectsCells, CulturedCollagen Type I/*biosynthesisDose-Response Relationship, DrugHumansLiver/*cytology/drug effects/metabolismOxidative Stress/drug effects/*physiologyProstaglandin D2/*analogs & derivatives/pharmacology
Abstract
15 deoxy-Delta(12,14)-prostaglandin(2) (15d-PGJ(2)) is known to inhibit the proliferation of hepatic stellate cells (HSCs), major cellular components that cause hepatic fibrosis, in vitro. It also induces oxidative stress, which results in hepatic myofibroblast death. On the other hand, oxidative stress generally induces HSC proliferation and collagen synthesis in vitro, and liver fibrogenesis in vivo. In this study, we evaluated the effects of 15d-PGJ(2) at various concentrations on the viability and collagen synthesis of HSCs. 15d-PGJ(2) increased intracellular reactive oxygen species (ROS), and reduced the viability of human HSCs at concentrations 5 microM by inducing apoptotic cell death. In addition, the antioxidants alpha-tocopherol and N-acetylcysteine (NAC) blocked 15d-PGJ(2)-induced HSC death. Collagen I synthesis was increased 1.5-fold by 0.5 microM 15d-PGJ(2) treatment, but was reduced to 30% of the control level by 10 microM 15d-PGJ(2), and NAC pretreatment prevented these changes in collagen production by 15d-PGJ(2). We conclude that 15d-PGJ(2) may either induce or prevent hepatic fibrogenesis depending on its concentration.
ISSN
0952-3278 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16098720

http://hdl.handle.net/10371/25980
DOI
https://doi.org/10.1016/j.plefa.2005.06.003
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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