Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Department of Medical Parasitology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Acta Biochim Biophys Sin (Shanghai). 2022 Sep 25;54(10):1421-1430. doi: 10.3724/abbs.2022130.
Egg granuloma formation in the liver is the main pathological lesion caused by infection, which generally results in liver fibrosis and may lead to death in advanced patients. MicroRNAs (miRNAs) regulate the process of liver fibrosis, but the putative function of miRNAs in liver fibrosis induced by . infection is largely unclear. Here, we detect a new miRNA, miR-182-5p, which shows significantly decreased expression in mouse livers after stimulation by soluble egg antigen (SEA) of . or . infection. Knockdown or overexpression of miR-182-5p causes the increased or decreased expression of tristetraprolin (TTP), an important immunosuppressive protein in the process of liver fibrosis. Furthermore, knockdown of miR-182-5p upregulates TTP expression and significantly alleviates . -induced hepatic fibrosis. Our data demonstrate that downregulation of miR-182-5p increases the expression of TTP in mouse livers following schistosome infection, which leads to destabilization of inflammatory factor mRNAs and attenuates liver fibrosis. Our results uncover fine-tuning of liver inflammatory reactions related to liver fibrosis caused by . infection and provide new insights into the regulation of schistosomiasis-induced hepatic fibrosis.
肝内卵肉芽肿的形成是 感染引起的主要病理学病变,通常导致肝纤维化,在晚期患者中可能导致死亡。microRNAs(miRNAs)调节肝纤维化的过程,但 miRNA 在 感染引起的肝纤维化中的潜在功能在很大程度上尚不清楚。在这里,我们检测到一种新的 miRNA,miR-182-5p,在 SEA 刺激或 感染后,其在小鼠肝脏中的表达显著降低。miR-182-5p 的敲低或过表达导致在肝纤维化过程中重要的免疫抑制蛋白 tristetraprolin(TTP)的表达增加或减少。此外,miR-182-5p 的敲低上调了 TTP 的表达,并显著缓解了 诱导的肝纤维化。我们的数据表明,在血吸虫感染后,miR-182-5p 的下调增加了小鼠肝脏中 TTP 的表达,导致炎症因子 mRNAs 的不稳定性,并减轻肝纤维化。我们的结果揭示了与 感染引起的肝纤维化相关的肝炎症反应的精细调控,并为血吸虫病诱导的肝纤维化的调控提供了新的见解。