烟曲霉胶霉毒素通过mTOR/STAT3信号通路调控人肺泡Ⅱ型上皮细胞自噬的机制研究OA
Mechanism of gliotoxin from Aspergillus fumigatus regulating autophagy in human alveolar type II epithelial cells via the mTOR/STAT3 signaling pathway
目的 研究胶霉毒素通过哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)/信号传导与转录活化因子(signal transducer and activator of transcription 3,STAT3)通路诱导人肺泡Ⅱ 型上皮细胞A549自噬的影响及其机制.方法 将A549细胞分为对照组、0.5 μmol/L、2 μmol/L和4 μmol/L胶霉毒素组,培养24 h.使用倒置显微镜观察细胞的生长状态;使用CCK-8法检测A549细胞的细胞活性.通过流式细胞术检测细胞内ROS含量和细胞凋亡率.Western blot 检测自噬相关蛋白以及 mTOR/STAT3 信号轴相关蛋白的表达水平.结果 与对照组比较,实验组 A549 细胞的增殖活性明显降低(P<0.001);2 μmol/L 组和 4 μmol/L 组的细胞内 ROS 含量、细胞凋亡率增高;MDC 染色显示实验组的荧光强度显著增强(P<0.001);2 μmol/L 和 4 μmol/L 组自噬相关蛋白 Beclin-1 和 LC3Ⅱ/LC3Ⅰ 表达增高(P<0.05),p62 的表达降低(P<0.05);p-mTOR/mTOR 和 p-STAT3/STAT3 蛋白表达水平降低(P<0.05).结论 胶霉毒素可影响人肺泡Ⅱ 型上皮细胞 A549 的增殖、凋亡,并诱导自噬,其作用可能与抑制mTOR/STAT3 信号通路的激活有关.
Objective Study on the effect and mechanism of gliotoxin-induced autophagy in human alveolar type Ⅱ epithelial cells via the mTOR/STAT3 pathway.Methods A549 cells were divided into control group,0.5 μmol/L,2 μmol/L,and 4 μmol/L gliotoxin-treated groups,and cultured for 24 hours.Cell growth status was observed using an inverted optical microscope.A549 cell viability was detected by CCK-8 assay.Intracellular ROS levels and apoptosis rate were measured by flow cytometry.The expression levels of autophagy-related proteins and mTOR/STAT3 signaling pathway-related proteins were analyzed by Western blot.Results Compared with the control group,the proliferative activity of A549 cells in the experimental group was significantly decreased.The 2 μmol/L and 4 μmol/L groups exhibited increased intracellular ROS levels and elevated apoptosis rates.MDC staining revealed significantly enhanced fluorescence intensity in the treated groups.The 2 μmol/L and 4 μmol/L groups showed increased expression of autophagy-related proteins Beclin-1 and LC3Ⅱ/LC3Ⅰ,while p62 expression was decreased.The protein expression levels of p-mTOR/mTOR and p-STAT3/STAT3 were significantly reduced.Conclusion Gliotoxin can inhibit proliferation,promote apoptosis,and induce autophagy in human alveolar type Ⅱ epithelial A549 cells,potentially through suppression of the mTOR/STAT3 signaling pathway activation.
李莎莎;杨绍兵;焦婷婷;苏明;师志云;郭雅琪
宁夏医科大学总医院医学实验中心,银川 750004||宁夏医科大学总医院宁夏临床病原微生物重点实验室,银川 75004宁夏医科大学总医院心血管内科,银川 750004宁夏医科大学总医院心脑血管病医院检验科,银川 750001宁夏医科大学总医院医学实验中心,银川 750004宁夏医科大学总医院医学实验中心,银川 750004宁夏医科大学总医院医学实验中心,银川 750004
自噬信号通路胶霉毒素肺泡Ⅱ型上皮细胞
autophagysignaling pathwaygliotoxintype II alveolar epithelial cells
《中国真菌学杂志》 2026 (2)
147-153,7
宁夏自然科学基金项目(2023AAC03531)
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