****博导糖尿病免疫研究获新成果

　　

生物通报道，中科院上海生命科学研究所营养科学研究所博导、研究员秦莹在最近一期的JBC上发表糖尿病预防研究的最新成果文章Berberine differentially modulates the activities of Erk, p38 MAPK and JNK to suppress Th17 and Th1 T cell differentiation in type 1 diabetic mice。

 

该项目得到了中科院“****”和上海市科委等基金的支持。

 

在该工作中，秦莹研究组发现黄连素可以延缓自身免疫性I型糖尿病小鼠模型NOD的发病。体外研究证实，黄连素抑制了Th17和Th1两群炎症性T细胞的分化，这一过程与黄连素差异性调节MAPK家族的各个激酶活性相关联。

 

生物通推荐原文摘要

Cui G, Qin X, Zhang Y, Gong Z, Ge B, Zang YQ.

Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, China;

 

Berberine, an alkaloid derivative from Berberis Vulgaris L, has been used extensively in traditional Chinese medicine to treat diarrhea and diabetes, but the underlying mechanisms for treating diabetes are not fully understood. Recent studies suggested that berberine has many beneficial biological effects, including anti-inflammation. Because type 1 diabetes is caused by T cell-mediated destruction of beta cells and severe islet inflammation, we hypothesized that berberine could ameliorate type 1 diabetes through its immune regulation properties. Here, we reported that 2 weeks of oral administration of berberine prevented the progression of type 1 diabetes in half of the NOD mice, and decreased Th17 and Th1 cytokine secretion. Berberine suppressed Th17 and Th1 differentiation by reducing the expression of lineage markers. We found that berberine inhibited Th17 differentiation by activating Erk1/2 and inhibited Th1 differentiation by inhibiting p38 MAPK and JNK activation. Berberine down-regulated the activity of STAT1 and STAT4 through the suppression of p38 MAPK and JNK activation, and controlled the stability of STAT4 through the ubiquitin-proteasome pathway. Our findings indicate that berberine targets MAPK to suppress Th17 and Th1 differentiation in type 1 diabetic NOD mice. This study revealed a novel role of Erk in Th17 differentiation through downregulation of STAT3 phosphorylaion and RORgammat expression.

 

秦莹    博士 研究员

 

应用营养学研究组长

个人简介：

        1984年毕业于上海第二医科大学，1993年获比利时林堡大学免疫学博士学位，曾任比利时威廉研究所肿瘤免疫研究组主任， 美国贝勒医学院讲师，助理教授。现任中国科学院上海生命科学院营养科学研究所研究员和研究组长。

 

研究方向：

        1. 通过调节核受体PPAR和LXR等转录因子的活性研究天然小分子改善肥胖、胰岛素耐受、糖尿病等代谢综合症的关键靶标及应用。

        2. 自身免疫性I型糖尿病等发病机理与免疫调节网络研究以及T细胞疫苗和免疫调节剂干预对Treg和Th1/Th17炎性细胞群的作用。

        3. 体外快速筛选和制备单克隆抗体平台。

近期论文：

 

Guoliang Cui, Xia Qin, Yuebo Zhang, Zhenwei Gong, Baoxue Ge, and Ying Q Zang. Berberine differentially modulates the activities of Erk, p38 MAPK and JNK to suppress Th17 and Th1 T cell differentiation in type 1 diabetic mice. J. Biol. Chem., Aug 2009; in press.

 

Yuebo Zhang, Cheng Huang, Xiaoyan Sheng, Zhenwei Gong and Ying Q Zang (秦莹). Lecithin promotes adipocyte differentiation and hepatic lipid accumulation. International Journal of Molecular Medicine, 2009; 23:449-454.

 

Guoliang Cui, Yuebo Zhang, Zhenwei Gong, Jingwu Z Zhang and Ying Q Zang. Induction of the CD4+CD25+Foxp3+ regulatory T cell response through interleukin-4 by Glatiramer Acetate in murine models of type I diabetes. Cell Research, 2009; 19:574-583.

 

Zhenwei Gong, Cheng Huang, Xiaoyan Sheng, Yuebo Zhang, Qunyi Li, Ming-Wei Wang, Linling Peng and Ying Q Zang. The role of Tanshinone IIA in the Treatment of Obesity through PPARγ Antagonism. Endocrinology, 2009; 150:104-13.

 

Xiaoyan Sheng, Yuebo Zhang，Zhenwei Gong, Cheng Huang and Ying Q Zang. Improved insulin resistance and lipid metabolism by cinnamon through activation of peroxisome proliferator-activated receptors. PPAR Research, Epub 2008; 2008:581348.

 

已申请的专利目录：

        1. 肉桂提取物的制备方法和肉桂提取物。

        2. 大黄治疗脂肪肝的作用机理。

        3. 丹参酮作为PPARg拮抗剂预防和治疗肥胖及代谢综合症。