近日，来自南京医科大学的研究人员在国际学术期刊scientific reports在线发表了一项最新研究进展，他们发现在克罗恩病中miR-19b会发生表达下调，并通过分析进一步证明miR-19b能够通过调节SOCS3表达抑制炎症应答，这一发现对于靶向microRNA治疗炎症性肠道疾病具有一定意义。

　　研究人员指出，在炎症性肠道疾病中常会发现microRNA的异常表达，但这些microRNA的生物学功能和靶向目标仍未得到完全了解。他们在该项研究中发现miR-19b在克罗恩病中表达显著下调，通过生物信息学分析，预测调节固有免疫和适应性免疫，并在多种免疫相关疾病中发挥重要作用的细胞因子信号抑制因子3（SOCS3）可能是miR-19b的一个潜在靶向目标。

　　研究人员利用克罗恩病病人的肠道组织样品进行分析，发现miR-19b的表达与SOCS3的蛋白水平呈负相关关系，但与mRNA并无此相关性，随后他们在caco2细胞和HT29细胞中进行了miR-19b的过表达和敲低实验，当在caco2细胞中过表达miR-19b能够显著抑制SOCS3 的表达，同时会导致MIP-3a的表达增加；与此相反，敲低miR-19b能够增加SOCS3表达，同时抑制MIP-3a，从而证实了miR-19b是SOCS3的一个直接调控因子，研究人员还通过荧光素酶报告基因实验，证明了miR-19b能够直接识别SOCS3的3`UTR，从而调节SOCS3的表达。

　　总的来说，这项研究发现miR-19b能够通过下调SOCS3，调节小肠上皮细胞趋化因子的合成，抑制炎症应答，对于治疗克罗恩病具有一定意义。

　　doi:10.1038/srep10397

　　miR-19b downregulates intestinal SOCS3 to reduce intestinal inflammation in Crohn's disease

　　Xiuqin Cheng,Xiaofei Zhang,Jiewen Su,Yingdi Zhang,Weimei Zhou,Jun Zhou,Cheng Wang,Hongwei Liang,Xi Chen,Ruihua Shi,Ke Zen,Chen-Yu Zhang&Hongjie Zhang

　　Although aberrant microRNA (miRNA) expression has frequently been observed in inflammatory bowel disease (IBD), its biological functions and targets remain largely unknown. Present study found that miR-19b was significantly downregulated in active Crohn's disease (CD). Using bioinformatics analysis, suppressor of cytokine signalling 3 (SOCS3), a physiological regulator of innate and adaptive immunity that controls several immuno-inflammatory diseases, was predicted to be a potential target of miR-19b. An inverse correlation between miR-19b and SOCS3 protein levels, but not mRNA, was identified in active-CD intestinal tissue samples. By overexpressing or knocking down miR-19b in Caco2 cells and HT29 cells, it was experimentally validated that miR-19b is a direct regulator of SOCS3. Using a luciferase reporter assay, it was confirmed that miR-19b directly recognizes the 3'-untranslated region (3'-UTR) of SOCS3. Furthermore, overexpression of miR-19b decreased SOCS3 expression, leading to increased production of macrophage-inflammatory protein-3α (MIP-3α) in Caco2 cells. In contrast, knockdown of miR-19b increased SOCS3 and decreased MIP-3α. Finally, intracolonically delivered miR-19b decreased the severity of colitis induced with 2,4,6-trinitrobenzene sulphonic acid (TNBS). Taken together, our findings suggest that miR-19b suppresses the inflammatory response by inhibiting SOCS3 to modulate chemokine production in intestinal epithelial cells (IECs) and thereby prevents the pathogenesis of CD.