Abstract
We previously demonstrated that astaxanthin (ASTX), a xanthophyll carotenoid, has an antifibrogenic effect in hepatic stellate cells (HSC), primarily responsible for the accumulation of extracellular matrix protein during the development of liver fibrosis. Studies have shown that microRNAs (miRNAs) are involved in HSC activation. Therefore, we analyzed the expression of 84 miRNAs using miRNA arrays in primary mouse quiescent HSC (qHSC) and activated HSC (aHSC) treated with/without ASTX during their activation. Compared with qHSC, the expression of 14 miRNAs and 23 miRNAs was increased and decreased by more than 2-fold, respectively, in aHSC. Among the 14 miRNAs increased in aHSC, the expression of miR-192-5p, miR-382-5p, and miR-874-3p was reduced by ASTX. In addition, ASTX increased the expression of miR-19a-3p, miR-19b-3p, and miR-101a-3p among 23 miRNAs decreased in aHSC. Moreover, we confirmed miR-382-5p expression was ~15-fold higher in aHSC than qHSC, and ASTX markedly inhibited the induction measured by quantitative real-time PCR. We identified that the expression of Baz1a and Zfp462 from the predicted miR-382-5p target genes was significantly reduced in aHSC while increased by ASTX treatment similar to the levels in qHSC. The roles of Baz1a and Zfp462 in HSC activation and the antifibrogenic effect of ASTX need to be further investigated.
Highlights
Liver fibrosis is characterized by excessive accumulation of extracellular matrix (ECM)proteins, including collagen [1]
Primary mouse quiescent HSC (qHSC) and activated HSC (aHSC) treated with or without ASTX during the activation Primary mouse qHSC and aHSC treated with or without ASTX during the activation were subjected to miRNA array analysis, which can detect 84 miRNAs known to be related were subjected to miRNA array analysis, which can detect 84 miRNAs known to be reto fibrosis (Supplemental Figure S1)
Primary mouse aHSC had increased expression of miR-382-5p by ~15-fold compared to qHSC, which was significantly reduced by ASTX treatment
Summary
Liver fibrosis is characterized by excessive accumulation of extracellular matrix (ECM). Proteins, including collagen [1]. The abnormal accumulation of ECM proteins in the liver distorts the liver architecture and further impairs hepatic function [2]. Liver fibrosis occurs in most chronic liver diseases by repeated or long-lasting liver injury [3]. Common causes of liver fibrosis include chronic hepatitis C infection, alcohol abuse, and nonalcoholic steatohepatitis (NASH) [3]. Hepatic stellate cells (HSC) play an essential role in developing liver fibrosis. HSC are present in the space between endothelial cells and hepatocytes, called
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
