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Serotonin-induced miR-221/222 contribute to the activation of hepatic stellate cells
Biologia ( IF 1.5 ) Pub Date : 2020-05-08 , DOI: 10.2478/s11756-019-00376-y
Yi Xiang , Yu-Shui Ma , Ji-Bin Liu , Zhi-Jun Wu , Xiao-Ping Wang , Li-Ping Liu , Gao-Ren Wang , Da Fu , Wei Shi

In the diseased liver, hepatic stellate cells (HSCs) transdifferentiate into “activated” myofibroblasts that then drive fibrogenesis by promoting the net deposition of extracellular matrix. This regulatory function requires stimulation of the 5-hydroxytryptamine 2B receptor (5-HT2B) on HSCs by serotonin (5-HT), which activates extracellular regulated protein kinases and the transcription factor JunD. However, the regulation mechanisms of 5-HT on microRNAs in the activation of HSCs need a thorough study. In this study, our data show that the expression of miR-221/222 increases with the stimulation of 5-HT and is correlated with the expression levels of alpha 1 type I collagen and α-smooth muscle actin in HSCs. Silencing against 5-HT2B attenuates miR-221/222 expression. Stimulation of stellate cells with 5-HT significantly upregulated miR-221/222 expression, while knockdown of JunD or treatment with the ERK inhibitor PD98059 significantly reduced miR-221/222 expression. miR-221 and miR-222 are potential targets in the quest for a cure for human liver fibrosis.



中文翻译:

5-羟色胺诱导的miR-221 / 222有助于肝星状细胞的活化

在患病的肝脏中,肝星状细胞(HSC)转分化为“活化的”成纤维细胞,然后通过促进细胞外基质的净沉积来驱动纤维化。这种调节功能需要通过血清素(5-HT)刺激HSC上的5-羟色胺2B受体(5-HT2B)来激活细胞外调节的蛋白激酶和转录因子JunD。但是,5-HT对HSC激活中microRNA的调控机制尚需深入研究。在这项研究中,我们的数据表明miR-221 / 222的表达随5-HT的刺激而增加,并且与HSC中α1型I胶原和α平滑肌肌动蛋白的表达水平相关。针对5-HT2B沉默可减弱miR-221 / 222的表达。用5-HT刺激星状细胞显着上调了miR-221 / 222的表达,而敲除JunD或用ERK抑制剂PD98059处理则显着降低了miR-221 / 222的表达。miR-221和miR-222是寻求治疗人类肝纤维化的潜在靶标。

更新日期:2020-05-08
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