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Abstract：
To investigate the role of the EGFR/MAPK signaling pathway in PM2.5 in promoting the MUC5AC hypersecretion in airway and exacerbating airway inflammation.
By establishing rat model exposed to PM2.5, overexpressing miR-133b-5p and Claudin1, the content of IL-1 and TNF-α in serum were detected by ELISA, the pathology of lung tissue was observed by HE staining, p-EGFR, Claudin1, MUC5AC, p-ERK1/2, p-JNK, p-p38 in rats lung tissue were detected by immunohistochemical and WB, the expression level of miR-133b-5p in rats lung tissue were detected by qPCR.
After the rats were exposed to PM2.5, the content of inflammatory factors in serum increased, the inflammatory damage of lung tissues occurred, the expression of miR-133b-5p was down-regulated, and the expression of MUC5AC protein was increased. The ELISA test results showed that the expression of IL-1 and TNF-α in the model group was significantly higher than that in the control group, and the model +AG1478 treatment group was down-regulated compared with the model group, and the +miR-133b-5p agomir treatment group was significantly lower than that in the control group, the model group and the model +Claudin1 overexpression blank load group, and the model +Claudin1 overexpression group was down-regulated compared with the model group and the model +Claudin1 overexpression blank load group. The protein detection results showed that the expression of p-EGFR, MUC5AC, p-ERK1/2, p-JNK and p-p38 proteins was increased and the expression of Claudin1 protein was decreased in the model group compared with the control group. In the model + AG1478 treatment group, model + miR-133b-5p agomir treatment group and model + Claudin1 overexpression group, compared with the model group, p-EGFR, MUC5AC, p-ERK1/2, p-JNK, p-p38 protein expression was down-regulated, and Claudin1 protein expression was up-regulated.
PM2.5 inhibited the expression of miR-133b-5p to activate the EGFR/MAPK signal pathway, induce the hypersecretion of MUC5AC, thus aggravating PM2.5-related airway inflammation in rats.
By establishing rat model exposed to PM2.5, overexpressing miR-133b-5p and Claudin1, the content of IL-1 and TNF-α in serum were detected by ELISA, the pathology of lung tissue was observed by HE staining, p-EGFR, Claudin1, MUC5AC, p-ERK1/2, p-JNK, p-p38 in rats lung tissue were detected by immunohistochemical and WB, the expression level of miR-133b-5p in rats lung tissue were detected by qPCR.
After the rats were exposed to PM2.5, the content of inflammatory factors in serum increased, the inflammatory damage of lung tissues occurred, the expression of miR-133b-5p was down-regulated, and the expression of MUC5AC protein was increased. The ELISA test results showed that the expression of IL-1 and TNF-α in the model group was significantly higher than that in the control group, and the model +AG1478 treatment group was down-regulated compared with the model group, and the +miR-133b-5p agomir treatment group was significantly lower than that in the control group, the model group and the model +Claudin1 overexpression blank load group, and the model +Claudin1 overexpression group was down-regulated compared with the model group and the model +Claudin1 overexpression blank load group. The protein detection results showed that the expression of p-EGFR, MUC5AC, p-ERK1/2, p-JNK and p-p38 proteins was increased and the expression of Claudin1 protein was decreased in the model group compared with the control group. In the model + AG1478 treatment group, model + miR-133b-5p agomir treatment group and model + Claudin1 overexpression group, compared with the model group, p-EGFR, MUC5AC, p-ERK1/2, p-JNK, p-p38 protein expression was down-regulated, and Claudin1 protein expression was up-regulated.
PM2.5 inhibited the expression of miR-133b-5p to activate the EGFR/MAPK signal pathway, induce the hypersecretion of MUC5AC, thus aggravating PM2.5-related airway inflammation in rats.
摘要：
目的：探讨PM2.5中EGFR/MAPK信号通路在促进气道MUC5AC高分泌、加重气道炎症中的作用。
方法：通过建立PM2.5、过表达miR-133b-5p和Claudin1的大鼠模型，用ELISA法检测血清中IL-1和TNF-α的含量。HE染色观察肺组织病理,p-EGFR,Claudin1,MUC5AC,p-ERK1/2,p-JNK,免疫组织化学和WB检测大鼠肺组织中p-p38,qPCR检测大鼠肺组织中miR-133b-5p的表达水平。
结果：大鼠暴露于PM2.5后，血清炎症因子含量升高，肺组织的炎症损伤发生，miR-133b-5p的表达下调，MUC5AC蛋白表达增加。ELISA检测结果显示,模型组IL-1和TNF-α的表达明显高于对照组,与模型组相比，模型+AG1478治疗组下调，+miR-133b-5p阿戈米尔治疗组明显低于对照组,模型组和模型+Claudin1过表达空白负载组，模型+Claudin1过表达组较模型组和模型+Claudin1过表达空白负荷组下调。蛋白检测结果显示,p-EGFR的表达,MUC5AC,与对照组相比，模型组p-ERK1/2、p-JNK和p-p38蛋白表达增加，Claudin1蛋白表达降低。在模型+AG1478治疗组中，模型+miR-133b-5p阿戈米尔治疗组和模型+Claudin1过表达组,与模型组相比，p-EGFR,MUC5AC,p-ERK1/2,p-JNK,p-p38蛋白表达下调，Claudin1蛋白表达上调。
结论：PM2.5通过抑制miR-133b-5p的表达激活EGFR/MAPK信号通路,诱导MUC5AC的高分泌，从而加重PM2.5相关大鼠气道炎症。
方法：通过建立PM2.5、过表达miR-133b-5p和Claudin1的大鼠模型，用ELISA法检测血清中IL-1和TNF-α的含量。HE染色观察肺组织病理,p-EGFR,Claudin1,MUC5AC,p-ERK1/2,p-JNK,免疫组织化学和WB检测大鼠肺组织中p-p38,qPCR检测大鼠肺组织中miR-133b-5p的表达水平。
结果：大鼠暴露于PM2.5后，血清炎症因子含量升高，肺组织的炎症损伤发生，miR-133b-5p的表达下调，MUC5AC蛋白表达增加。ELISA检测结果显示,模型组IL-1和TNF-α的表达明显高于对照组,与模型组相比，模型+AG1478治疗组下调，+miR-133b-5p阿戈米尔治疗组明显低于对照组,模型组和模型+Claudin1过表达空白负载组，模型+Claudin1过表达组较模型组和模型+Claudin1过表达空白负荷组下调。蛋白检测结果显示,p-EGFR的表达,MUC5AC,与对照组相比，模型组p-ERK1/2、p-JNK和p-p38蛋白表达增加，Claudin1蛋白表达降低。在模型+AG1478治疗组中，模型+miR-133b-5p阿戈米尔治疗组和模型+Claudin1过表达组,与模型组相比，p-EGFR,MUC5AC,p-ERK1/2,p-JNK,p-p38蛋白表达下调，Claudin1蛋白表达上调。
结论：PM2.5通过抑制miR-133b-5p的表达激活EGFR/MAPK信号通路,诱导MUC5AC的高分泌，从而加重PM2.5相关大鼠气道炎症。
