华北理工大学公共卫生学院;河北省器官纤维化重点实验室;成都中医药大学医学技术学院;
目的 探究溴结构域蛋白4(BRD4)在转化生长因子-β1(TGF-β1)诱导的肺泡Ⅱ型上皮细胞间质转化中的作用机制。方法 采用不同浓度(5、10 ng/ml)的TGF-β1刺激MLE-12细胞48 h建立上皮间质转化(EMT)细胞模型，并对细胞予以50 nmol/L BRD4抑制剂JQ-1,100μmol/L高迁移率族蛋白B1(HMGB1)抑制剂甘草甜素(GA)和3μg/ml的重组高迁移率族蛋白1(rHMGB1)预处理。实验分组为：对照组、TGF-β1组、JQ-1组、JQ-1+TGF-β1组、GA组、GA+TGF-β1组、JQ-1+TGF-β1+rHMGB1组。采用CCK-8法检测JQ-1对细胞活力的影响；采用Western blot检测CDH1、ZO-1、Vimentin、α-SMA、BRD4、HMGB1、TGF-β1及Smad2/3、p-Smad2/3的蛋白表达水平；通过划痕实验检测细胞迁移能力。结果 与对照组比较，TGF-β1组Vimentin、α-SMA蛋白表达增加，CDH1和ZO-1蛋白表达降低，提示EMT模型构建成功。在该模型中，BRD4、HMGB1的表达明显增加。不同浓度的JQ-1均可抑制MLE-12的细胞活力，且呈浓度依赖性。JQ-1和GA均可缓解TGF-β1诱导的EMT的发生，并抑制由TGF-β1引起的HMGB1表达的增加和TGF-β1/Smad2/3通路的激活，而采用rHMGB1上调HMGB1的表达可以减少JQ-1对EMT和TGF-β1/Smad2/3通路的影响。此外，JQ-1和GA均可以有效降低TGF-β1诱导的细胞迁移；而rHMGB1可以缓解JQ-1对细胞迁移速率的抑制作用。结论 BRD4可通过影响HMGB1/TGF-β1/Smad2/3信号通路调控肺泡Ⅱ型上皮细胞向间质转化过程，且BRD4可能成为抑制肺纤维化的一个潜在靶点。
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2025.02.009
中图分类号:R563
引用信息:
[1]陈茹茹,韩璐,何海兰等.BRD4通过HMGB1/TGF-β1/Smad通路参与调控肺泡上皮细胞间质转化[J].安徽医科大学学报,2025,60(02):247-254.DOI:10.19405/j.cnki.issn1000-1492.2025.02.009.
基金信息:
国家自然科学基金(编号：81602814); 河北省自然科学基金(编号：H2017209154); 河北省高等学校科学技术研究项目(编号：BJ2017006)~~