Astaxanthin Attenuates the Changes in the Expression of MicroRNAs Involved in the Activation of Hepatic Stellate Cells

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.

Automated summary

We found that astaxanthin has an inhibitory effect on the activation of hepatic stellate cells, exerting its antifibrogenic effect through regulating the expression of miRNAs. Specifically, miR-382-5p is significantly upregulated in activated hepatic stellate cells, and this upregulation is inhibited by astaxanthin. Baz1a and Zfp462 may be target genes of miR-382-5p, and further investigation is needed to understand their roles in the activation of hepatic stellate cells and the antifibrogenic effect of astaxanthin.