HMGB1/RAGE信号通路参与尼古丁调控支气管上皮细胞TGF-β1和FGF-2的分泌  

Nicotine induces the secretion of TGF-β1 and FGF-2 via HMGB1/RAGE in human airway epithelial cells

作　　者：邹威凤[1] 王晓茜 盛青[1] 周晓婷[1] 黎希[1] Zou Weifeng;Wang Xiaoqian;Sheng Qing;Zhou Xiaoting;Li Xi(Department of Respiratory Medicine,Guangzhou Chest Hospital,Guangzhou 510000,China)

机构地区：[1]广州市胸科医院呼吸科,510000

出　　处：《国际呼吸杂志》2020年第5期368-372,共5页International Journal of Respiration

基　　金：广东省自然基金项目(2015A030310378、2016A030313422);广州市卫生和计划生育科技项目(20161A011034)。

摘　　要：目的本研究旨在探讨尼古丁是否通过高迁移率族蛋白1(HMGB1)/晚期糖基化终产物受体(RAGE)信号通路调控支气管上皮细胞转化生长因子β1(TGF-β1)和成纤维细胞生长因子2(FGF-2)的分泌。方法尼古丁(6×10^-6 mol/L)刺激支气管上皮细胞株16HBE,采用酶联免疫吸附测定法(ELISA)检测刺激24 h后细胞中HMGB1、TGF-β1和FGF-2分泌,Western blotting方法检测RAGE表达。预先加入HMGB1 siRNA孵育48 h或RAGE中和抗体孵育1 h,再加入尼古丁刺激16HBE 24 h,ELISA法检测HMGB1、TGF-β1和FGF-2的分泌,Western blotting方法检测RAGE的表达。结果尼古丁刺激24 h后HMGB1的分泌和RAGE的表达量较未予尼古丁刺激的正常对照组明显增加,TGF-β1和FGF-2的分泌量也显著增加。加入HMGB1 siRNA后尼古丁刺激24 h组,HMGB1的分泌量较单纯尼古丁刺激组明显减少,RAGE的表达量显著减少,同时TGF-β1和FGF-2的分泌量较单纯尼古丁刺激组显著减少。加入RAGE中和抗体后尼古丁刺激24 h组,TGF-β1和FGF-2的分泌量较单纯尼古丁刺激组显著减少。结论HMGB1/RAGE信号通路参与了尼古丁调控支气管上皮细胞TGF-β1和FGF-2的分泌。Objective To test whether nicotine induces the secretion of transforming growth factor-β1(TGF-β1)and fibroblast growth factor 2(FGF-2)in HBECs in vitro via the high mobility group protein B1(HMGB1)/receptor for advanced glycation end products(RAGE)signaling pathway.Methods Cultured HBECs were exposed to nicotine(6×10^-6 mol/L)for 24 h.The secretion of HMGB1,TGF-β1 and FGF-2 was assessed by ELISA,the expression of RAGE was assessed by Western blotting.HBECs were either transfected with a small interfering RNA(siRNA)targeting HMGB1 for 48 h or incubated with anti-RAGE antibodies for 1 h and subsequently stimulated with nicotine for 24 h,then the secretion of HMGB1,TGF-β1 and FGF-2 was assessed by ELISA,the expression of RAGE was assessed by Western blotting.Results We showed that cells exposed to nicotine for 24 h exhibited significantly increased HMGB1,TGF-β1 and FGF-2 secretion and RAGE expression.The HMGB1 siRNA prevented these effects.Furthermore,anti-RAGE antibodies significantly decreased the secretion of TGF-β1 and FGF-2 from HBECs.Conclusions These results suggest that nicotine induces the secretion of TGF-β1 and FGF-2 in HBECs via the HMGB1/RAGE signaling pathway.

关 键 词：尼古丁 转化生长因子β1 成纤维细胞生长因子2 气道上皮细胞 高迁移率族蛋白1/晚期糖基化终产物受体 

分 类 号：R5[医药卫生—内科学]