rSjP40 protein promotes PPARγ expression in LX‐2 cells through microRNA‐27b

Abstract

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.

Upregulation of KSRP by miR‐27b attenuates schistosomiasis‐induced hepatic fibrosis by targeting TGF‐β1

“…Xing et al reported that sustained elevation of miR‐203‐3p in liver could attenuate Schistosome‐induced hepatic fibrosis . It has been reported that rSjP40 protein (the recombinant P40 protein from S. japonicum ) promotes PPARγ expression in LX‐2 cells through miR‐27b, thus inhibits the activation of HSCs . Our studies found a new mechanism underlying inhibition of HSCs activation by miR‐27b.…”

“…34 It has been reported that rSjP40 protein (the recombinant P40 protein from S. japonicum) promotes PPARγ expression in LX-2 cells through miR-27b, thus inhibits the activation of HSCs. 35 Our studies found a new mechanism underlying inhibition of HSCs activation by miR-27b. Our data indicated that miR-27b regulates the mRNA stability of TGF-β1 to regulate HSCs activation through targeting KSRP expression, which may represent new insights into the pathogenesis of schistosomiasis.…”

The Roles and Mechanisms of lncRNAs in Liver Fibrosis

“…It has been demonstrated that Gm5091 plays an important role in reactive oxygen species (ROS) levels, negatively regulating cell migration, interleukin-1β (IL-1β) secretion, and the expression of collagen I and mouse HSC activation markers, including α-SMA and desmin. It is widely considered that miR-27, miR-24, and miR-23 can promote progression to liver fibrosis through HSC differentiation and proliferation by activating smad4 and TGF-β [77,78]. As a new regulator of alcoholic hepatic fibrosis progression, sponging of miR-27b/23b/24 by lncRNA Gm5091 alleviates mouse alcoholic hepatic fibrosis and thereby increases TGF-β levels [19].…”

“…To date, it has been found that lncRNAs cooperate with the TGF-β signalling pathway to regulate HSC activation and hepatic fibrosis. Inhibition of lncRNAs (HIF1A-AS [48], Gm5091 [77,78], and lincRNA-p21 [53]) and overexpression of lncRNAs (MALAT1 [92], SCARNA10 [51], Lnc-LFAR1 [34], and HOTTIP [61]) involved in the TGF-β signalling pathway could promote HSC activation and subsequently induce hepatic fibrosis. Thus, lncRNAs can reveal the mechanism by which the TGF-β signalling pathway is involved in regulating liver fibrosis based on noncoding RNAs.…”

Investigating the potential of circulating microRNAs as non-invasive biomarkers in cirrhosis and hepatocellular carcinoma

“…444 Furthermore, an inverse correlation has also been described with PPARγ, with high miRNA-27b-3p levels identified alongside low PPARγ expression levels in a rat fibrosis model. 445 PPARγ was also identified as functional target of miRNA-27b-3p 446 and evidence of decreased PPARγ expression in a human hepatic stellate cell line 446 suggests a potential link with fibrosis. In other models, such as a mouse model of liver injury investigating bone marrow derived macrophages, miRNA-27b-3p expression was linked to the inhibition of macrophage activation in chronic liver injury through the 15d-PGJ2/PPARγ axis.…”