microRNA‐146a is involved in rSjP40‐inhibited activation of LX‐2 cells by targeting Smad4 expression

Abstract

Previous studies have demonstrated that the recombinant Schistosoma japonicum protein P40 (rSjP40) could inhibit activation of hepatic stellate cells (HSCs) through the TGF-β1/Smads signaling pathway. Since multiple microRNAs could play essential roles in HSC activation and in the process of hepatic fibrosis through targeting Smads, we attempted to seek the potential microRNAs that could be involved in rSjP40-induced inhibition of HSC activation. Using the method of quantitative real-time PCR, we found that rSjP40 could induce miR-146a expression in LX-2 cells. The down-regulated expression levels of Smad4 and α-SMA in LX-2 cells induced by rSjP40 were partially restored by an miR-146a inhibitor. miR-146a can be involved in rSjP40-induced inhibition of HSC activation through targeting Smad4. These findings provide us a new idea to explore the potential mechanisms by which rSjP40 could regulate the process of hepatic fibrosis.

Mechanisms and application strategies of miRNA‑146a regulating inflammation and fibrosis at molecular and cellular levels (Review)

“…Knockdown of the lncRNA MALAT1 affected inflammation by increasing miR-146a expression in an LPS-induced acute lung injury model (177). The recombinant Schistosoma japonicum protein P40 increased the levels of miR-146a in LX-2 cells and attenuated hepatic fibrosis LFH, ligamentum flavum hypertrophy; hUCMSC-EVs, human umbilical cord mesenchymal stromal cell-derived extracellular vesicles; HLSCs-EVs, human liver stem cell-derived extracellular vesicles; PEG-PLA, polyethylene glycol-poly(lactic acid); SCCII, severe controlled cortical impact injury; NLRP3, NACHT, LRR and PYD domains-containing protein 3; NEC, necrotizing enterocolitis; hUMSC-Exos, human umbilical cord mesenchymal stem cell-derived exosomes; IRI, ischemia/reperfusion injury; hUSC-Exo, human urine-derived stem cell-derived exosomes; IRAK1, interleukin-1 receptor-associated kinase 1; TRAF6, tumor necrosis factor receptor-associated factor 6; SMA, smooth muscle actin; Col-1, collagen I. by targeting Smad4 (178). Most drugs are designed according to miR-146a function by targeting the promoter of miR-146a, while lncRNAs act via their sponging effect.…”

“…Knockdown of the lncRNA MALAT1 affected inflammation by increasing miR-146a expression in an LPS-induced acute lung injury model ( 177 ). The recombinant Schistosoma japonicum protein P40 increased the levels of miR-146a in LX-2 cells and attenuated hepatic fibrosis by targeting Smad4 ( 178 ). Most drugs are designed according to miR-146a function by targeting the promoter of miR-146a, while lncRNAs act via their sponging effect.…”

rSjP40 Inhibited the Activity of Collagen Type I Promoter via Ets-1 in HSCs

“…The main pathogenesis of schistosomiasis is the occurrence of egg granuloma in the liver and intestinal wall, which can lead to severe enterohepatic fibrosis ( Duan et al, 2014 ). Soluble egg antigen (SEA) contains a variety of antigen components and Schistosoma japonicum protein P40 (SjP40) is one of the main components in the SEA, which belongs to the heat shock protein family of schistosomiasis ( Zhu et al, 2018 ). Previous studies in our lab have shown that SEA from Schistosoma japonicum could inhibit the expression of COL1A1 in activated HSCs ( Duan et al, 2014 ).…”