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Scientific reports:中国科学家发现克罗恩病潜在治疗靶点

  1. microRNA
  2. 克罗恩病

来源:生物谷 2015-05-27 18:01

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,病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。
                                                                       

2015年5月27日讯 /生物谷BIOON/ --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。(生物谷Bioon.com)
 
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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.
 
 
 

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