南方医科大学学报2017，Vol.37Issue(10)：1301-1307,7.DOI:10.3969/j.issn.1673-4254.2017.10.04
晚期糖基化终末产物受体促进甲苯二异氰酸脂哮喘小鼠MUC5AC表达及气道黏液高分泌
Receptor for advanced glycation end products upregulates MUC5AC expression and promotes mucus overproduction in mice with toluene diisocyanate-induced asthma
摘要
Abstract
Objective To explore the role of the receptor for advanced glycation end products (RAGE) in regulating the expression of MUC5AC and mucus production in a mouse model of toluene diisocyanate (TDI)-induced asthma. Methods BALB/c mice were randomly divided into control group, vehicle (AOO) group, TDI-induced asthma group and RAGE inhibitor (FPS-ZM1) group. PAS staining, Western blotting, and immunohistochemistry were used to analyze the changes in mucus production and MUC5AC expression in the airway of the mice, and the expression of p-ERK was detected with Western blotting. In vitro cultured human bronchial epithelial cell line 16HBE was transfected with lentiviral vector carrying short hairpin RNA targeting RAGE (shRNA-RAGE) and subsequently challenged with a TDI-human serum albumin (TDI-HSA)conjugate,and the changes in cellular MUC5AC mRNA expression as detected using RT-PCR;the protein expressions of ERK and p-ERK in the cells were examined with Western blotting. The effect of ERK inhibitor U0126 pretreatment on MUC5AC mRNA expression was also analyzed in the cells.Results Compared with the control mice,TDI-induced asthmatic mice showed significantly higher rates of PAS positivity and increased MUC5AC and p-ERK expressions in the airway (P<0.05). Treatment with FPS-ZM1 significantly decreased PAS positivity and lowered MUC5AC and p-ERK expressions in the airway of the asthmatic mice(P<0.05).Exposure of 16HBE cells to TDI-HSA caused a significant increase in MUC5AC mRNA expression and p-ERK protein expression (P<0.05), while RAGE knockdown obviously suppressed TDI-HSA-induced upregulation of p-ERK and MUC5AC mRNA(P<0.05). Treatment with the ERK inhibitor U0126 also lowered TDI-HSA-induced up-regulation of MUC5AC mRNA in the cells (P<0.05). Conclusion RAGE signaling induces MUC5AC expression via extracellular signal-regulated kinase pathway to promote mucus overproduction in mice with TDI-induced asthma.关键词
甲苯二异氰酸酯哮喘/晚期糖基化终末产物受体/MUC5AC/p-ERKKey words
toluene diisocyanate/asthma/receptor for advanced glycation end products/MUC5AC/p-ERK引用本文复制引用
熊婧,赵文驱,黄国华,姚利红,董航明,余常辉,赵海金,蔡绍曦..晚期糖基化终末产物受体促进甲苯二异氰酸脂哮喘小鼠MUC5AC表达及气道黏液高分泌[J].南方医科大学学报,2017,37(10):1301-1307,7.基金项目
国家自然科学基金(81670026) （81670026）
国家重点研发计划精准医学研究 发 展 计 划(2016YFC0905800) （2016YFC0905800）
广东省自然科学基金(2015A030313236) （2015A030313236）
广东省科技计划项目(2016A020215117) Supported by National Natural Science Foundation of China(81670026). （2016A020215117）
