Browse

Synergistic antifibrotic efficacy of statin and protein kinase C inhibitor in hepatic fibrosis

Cited 0 time in Web of Science Cited 0 time in Scopus
Authors
Yang, Jong In; Yoon, Jung-Hwan; Bang, Yung-Jue; Lee, Sung-Hee; Byun, Hee Jin; Kim, Won; Lee, Hyo-Suk; Myung, Sun-Jung; Lee, Soo-Mi
Issue Date
2010-01
Publisher
AMER PHYSIOLOGICAL SOC
Citation
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY; Vol.298 1; G126-G132
Keywords
liver fibrosispravastatinapoptosisenzastaurin
Abstract
Yang JI, Yoon J-H, Bang Y-J, Lee S-H, Lee S-M, Byun HJ, Myung S-J, Kim W, Lee H-S. Synergistic antifibrotic efficacy of statin and protein kinase C inhibitor in hepatic fibrosis. Am J Physiol Gastrointest Liver Physiol 298: G126-G132, 2010. First published November 12, 2009; doi:10.1152/ajpgi.00299.2009.-Statinhas antifibrotic efficacy in human fibrosing diseases, such as pulmonary and renal fibrosis, and is therefore implicated in hepatic fibrosis. However, statin can also activate protein kinase C (PKC), which augments hepatic fibrogenesis and is thereby likely to reduce the antifibrotic efficacy of statin. This study was designed to explore the hypothesis that simultaneous treatment with statin and PKC inhibitor may synergistically enhance antifibrotic efficacy in hepatic fibrosis. Hepatic fibrosis models were established in BALB/c mice by intraperitoneal injection of carbon tetrachloride or thioacetamide for 6 wk. Pravastatin and enzastaurin (PKC inhibitor) were administered by gavage for 5 wk. Cellular apoptosis was explored using 4`,6-diamidino-2-phenylindole or terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labeling (TUNEL) staining and immunoblot analysis. Hepatic fibrosis and hepatic stellate cell (HSC) activation were assessed by morphometric analysis of histological findings and immunohistochemistry for alpha-smooth muscle actin. In vitro, the addition of PKC inhibitor significantly increased statin-induced LX-2 cell apoptosis by enhancing the activation of mitochondrial apoptotic signals. TUNEL-positive HSCs were significantly increased in mice treated with statin + PKC inhibitor compared with those in control or single compound-treated mice. The percentage of area occupied by activated HSCs and the extent of collagen deposition were significantly decreased in mice treated with statin + PKC inhibitor compared with those in control or statin-treated mice. In conclusion, simultaneous treatment with statin and PKC inhibitor synergistically enhanced the antifibrotic efficacy in both in vitro and in vivo models of hepatic fibrosis and may therefore have therapeutic implication for reducing hepatic fibrosis.
ISSN
0193-1857
Language
English
URI
http://hdl.handle.net/10371/76557
DOI
https://doi.org/10.1152/ajpgi.0299.2009
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse