Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, China.
Nanjing Red Cross Blood Center, Nanjing, China; and.
FASEB J. 2018 Sep;32(9):4798-4803. doi: 10.1096/fj.201700520RR. Epub 2018 Apr 2.
miR-27b is reported to participate in the proliferation and differentiation of hepatic stellate cells (HSCs) and to regulate fat metabolism of rat HSCs by targeting retinoid X receptor α. Our previous study also indicated that the recombinant P40 protein from Schistosoma japonicum (rSjP40) inhibited the activation of HSCs. In this study, we observed the expression of miR-27b in rSjP40-treated LX-2 cells and explored its potential mechanisms. Quantitative real-time PCR showed that rSjP40 inhibits the expression of miR-27b in LX-2 cells. Further results obtained by Western blot and dual-luciferase reporter assay confirmed that miR-27b regulates peroxisome proliferator-activated receptor γ (PPARγ) expression in rSjP40-treated LX-2 cells by targeting the 3'-UTR of PPARγ. 5-AZA-2'-deoxycytidine (5-AZA-dC), which inhibits methylation of HSCs, partially reversed rSjP40-induced down-regulation expression of miR-27b in LX-2 cells. 5-AZA-dC also partially reversed rSjP40-induced up-regulation expression of PPARγ in LX-2 cells. The increased expression of PPARγ in rSjP40-treated LX-2 cells may be partially due to miR-27b methylation. Therefore, our study provides further insight into the mechanism by which rSjP40 inhibits HSC activation and provides a basis for future study of the blocking effect of rSjP40 in liver fibrosis.-Zhu, D., Lyu, L., Shen, P., Wang, J., Chen, J., Sun, X., Chen, L., Zhang, L., Zhou, Q., Duan, Y. rSjP40 protein promotes PPARγ expression in LX-2 cells through microRNA-27b.
miR-27b 据报道参与肝星状细胞（HSCs）的增殖和分化，并通过靶向视黄酸 X 受体 α 调节大鼠 HSCs 的脂肪代谢。我们之前的研究还表明，日本血吸虫重组 P40 蛋白（rSjP40）抑制 HSCs 的激活。在这项研究中，我们观察了 rSjP40 处理的 LX-2 细胞中 miR-27b 的表达，并探讨了其潜在机制。实时定量 PCR 显示 rSjP40 抑制 LX-2 细胞中 miR-27b 的表达。进一步通过 Western blot 和双荧光素酶报告基因检测证实，miR-27b 通过靶向 PPARγ 的 3'-UTR 调节 rSjP40 处理的 LX-2 细胞中过氧化物酶体增殖物激活受体 γ（PPARγ）的表达。5-氮杂-2'-脱氧胞苷（5-AZA-dC）抑制 HSCs 的甲基化，部分逆转 rSjP40 诱导的 LX-2 细胞中 miR-27b 的下调表达。5-AZA-dC 也部分逆转 rSjP40 诱导的 LX-2 细胞中 PPARγ 的上调表达。rSjP40 处理的 LX-2 细胞中 PPARγ 的表达增加可能部分归因于 miR-27b 的甲基化。因此，本研究进一步深入了解了 rSjP40 抑制 HSC 激活的机制，并为 rSjP40 抑制肝纤维化的阻断作用的进一步研究提供了依据。
