Detailed Information

Cited 0 time in webofscience Cited 0 time in scopus
Metadata Downloads

Improved anti-fibrotic effects by combined treatments of simvastatin and NS-398 in experimental liver fibrosis modelsopen access

Authors
Kang, Seong HeeYim, Hyung JoonHwang, Ji-wonKim, Mi-jungLee, Young-SunJung, Young KulYim, HyungshinKim, Baek-HuiPark, Hae-ChulSeo, Yeon SeokKim, Ji HoonYeon, Jong EunUm, Soon HoByun, Kwan Soo
Issue Date
Jul-2022
Publisher
대한내과학회
Keywords
Liver cirrhosis; Hydroxymethylglutaryl-CoA reductase inhibitors; Cyclooxygenase 2 inhibitors; Hepatic stellate cells
Citation
The Korean Journal of Internal Medicine, v.37, no.4, pp.745 - 756
Indexed
SCIE
SCOPUS
KCI
Journal Title
The Korean Journal of Internal Medicine
Volume
37
Number
4
Start Page
745
End Page
756
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/61212
DOI
10.3904/kjim.2021.138
ISSN
1226-3303
Abstract
Background/Aims Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti-fibrotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti-fibrotic effects. Methods The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, were investigated using an immortalized human hepatic stellate cell line (LX-2) and a hepatic fibrosis mouse model developed using thioacetamide (TAA) in drinking water. Cellular proliferation was investigated via 5-bromo-2-deoxyuridine uptake. Pro- and anti-apoptotic factors were investigated through Western blotting and real-time polymerase chain reaction analysis. Results The evaluation of the anti-proliferative effects on LX-2 cells showed that the observed effects were more pronounced with combination therapy than with single-drug therapy. Moreover, hepatic fibrosis and collagen deposition decreased significantly in TAA-treated mice in response to the combined treatment strategy. The mechanisms underlying the anti-fibrotic effects of the combination therapy were investigated. The effects of the combination therapy were correlated with increased expression levels of extracellular signal-regulated kinase 1/2 signaling molecules, upregulation of the Bax/Bcl-2 signaling pathway, inhibition of the transforming growth factor-β signaling pathway, and inhibition of tissue inhibitor of matrix metalloproteinases 1 and 2. Conclusions The combination of simvastatin and NS-398 resulted in a synergistic anti-fibrotic effect through multiple pathways. These findings offer a theoretical insight into the possible clinical application of this strategy for the treatment of advanced liver diseases with hepatic fibrosis.
Files in This Item
There are no files associated with this item.
Appears in
Collections
3. Graduate School > Biomedical Research Center > 1. Journal Articles
2. Clinical Science > Department of Pathology > 1. Journal Articles
2. Clinical Science > Department of Gastroenterology and Hepatology > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher Byun, Kwan Soo photo

Byun, Kwan Soo
Guro Hospital (Department of Gastroenterology and Hepatology, Guro Hospital)
Read more

Altmetrics

Total Views & Downloads

BROWSE