Gab2在SHP-2激活突变导致的小鼠肥大细胞异常增殖活化及其导致器官损伤中的作用.docVIP

  Gab2 在 SHP-2 激活突变导致的小鼠肥大细 胞异常增殖活化及其导致器官损伤中的 作用# 5 10 15 陈吉1，陈卓1，汪心怡1，郑红1，瞿成奎1,2，汪思应1** （1. 安徽医科大学基础医学院，合肥 230032； 2. Case Western Reserve University,Cleveland,USA,44106） 摘要：本研究观察接头蛋白 Gab2 对激活突变 SHP-2 导致的肥大细胞异常增殖活化是否具有 调控作用，对激活突变 SHP-2 小鼠器官损伤有无影响。用 Gab-2-/-、SHP-2D61G/+小鼠杂交建 立四种基因型(SHP-2+/+、Gab2-/-、SHP-2D61G/+、SHP-2D61G/+/Gab2-/-)小鼠为研究对象；取小 鼠骨髓细胞用 IL-3 诱导建立肥大细胞，用 MTS 法检测不同基因型小鼠肥大细胞对细胞因子 刺激增殖反应性；用 ELISA 法检测小鼠血清及肥大细胞分泌炎症因子水平，放射免疫法检 测小鼠血清中丙氨酸转氨酶(ALT)和心肌肌钙蛋白 I(cTnI)的水平；用病理组织学技术检测 小鼠组织白细胞浸润及器官损伤情况。结果表明，Gab2 缺失后，SHP-2 激活突变导致的小 鼠肥大细胞异常增殖及活化现象明显改善，对细胞因子增殖反应性下降，相应细胞因子分 泌减少，器官损伤减轻。结论：Gab2 缺失降低了 SHP-2 激活突变导致的小鼠肥大细胞异常 增殖活化和器官损伤。 关键词：SHP-2；Gab-2；肥大细胞异常增殖及活化；器官损伤 中图分类号：R363 20 Gab2 in relation to abnormal proliferation and activation in the mice mast cell and organ impairment induced by activating mutant SHP-2 tyrosine phosphatase CHEN Ji1, CHEN Zhuo1, WANG Xinyi1, ZHENG Hong1, QU Chengkui1,2, 25 30 35 40 WANG Siying1 (1. School of Basic Medical Sciences,Anhui Medical University, HeFei 230032; 2. Case Western Reserve University,Cleveland,44106,USA) Abstract: This study was purposed to investigate the roles of adaptor protein Gab2 in mast cell abnormal proliferation, activation,and organ damage in SHP-2D61G/+ mutant mice. Four kinds of mouse model genotyped as WT, Gab2-/-, SHP-2D61G/+, SHP-2D61G/+/Gab2-/- were generated from crossbreeding of Gab2-/- and SHP-2D61G/+ mouse. Mouse mast cell was generated from bone marrow cell induced by IL-3, and the proliferation of different genotype mast cells stimulated with cytokine was analyzed by MTS assay; Inflammatory cytokines levels in mouse serum and mast cell secretion were measured by ELISA, and alanine aminotransferase (ALT) and cardiac troponin I (cTnI) levels in serum was determined by radioimmunoassay; leukocyte infiltration in mouse tissues and organ impairment were detected with histopathologic detection. The results showed that Gab2 knockout reduced the mice mast cell abnormal proliferation and activation induced by SHP-2