时间标签：数据日期 2026-11-05 · 生成时间 2026-11-05 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 ｜ 情报发生日期 2026-11-05
研究问题
Whether CLDN18 expression changes in VILI or is involved in alveolar epithelial EMT has not been reported.Yes‐associated protein (YAP) is a key transcriptional coactivator of the Hippo pathway [10, 11].；Whether TM9SF1 regulates CLDN18 protein stability through autophagy has not been investigated.Therefore, this study focused on examining the role and underlying mechanisms of CLDN18 in alveolar epithelial EMT during VILI.；This indicates that VILI modeling induces lung injury, inflammation, fibrosis, alveolar epithelial EMT, and decreases CLDN18 expression.3.2Overexpression of CLDN18 Alleviates VILI and EMTTo investigate whether CLDN18 participates in VILI pathogenesis, AAV‐CLDN18 was delivered to mice via the tail vein.
方法
In clinical settings, high tidal volume ventilation induces VILI [3], especially in high‐risk patients or those with acute respiratory distress syndrome (ARDS) [4].；Mice lacking claudin 18 (CLDN18) showed impaired alveolar epithelial barrier function due to defective apical TJs [7], suggesting that CLDN18 may be an alveolar‐specific barrier regulator.；CLDN18 deficiency also induces type II alveolar epithelial cell proliferation and pulmonary enlargement in mice [8].
核心结论
Our data demonstrated that TM9SF1 promoted autophagic degradation of CLDN18, leading to YAP activation and subsequent EMT, and identified the TM9SF1‐CLDN18‐YAP axis as a potential therapeutic target for VILI.2Methods2.1Animal Experiment10‐week‐old male C57BL/6 mice were purchased from Hunan SJA Laboratory Animal Co.；This indicates that VILI modeling induces lung injury, inflammation, fibrosis, alveolar epithelial EMT, and decreases CLDN18 expression.3.2Overexpression of CLDN18 Alleviates VILI and EMTTo investigate whether CLDN18 participates in VILI pathogenesis, AAV‐CLDN18 was delivered to mice via the tail vein.；This indicates that CLDN18 overexpression attenuates VILI‐induced lung injury, inflammation, fibrosis, and alveolar epithelial EMT.Figure 2Overexpression of CLDN18 attenuates VILI and EMT.
局限
However, the upstream molecular mechanisms regulating alveolar epithelial EMT in VILI remain unclear.Claudins (CLDNs) are transmembrane proteins that form TJs and maintain epithelial polarity and the integrity of TJ barrier.；Existing studies have shown that TM9SF1 knockout significantly upregulates LC3‐II and downregulates p62 expression in a lipopolysaccharide (LPS)‐induced ALI mouse model, suggesting enhanced autophagic activity accompanied by reduced inflammation [16].However, this finding appears to contradict the mechanism reported in that study, in which TM9SF1 knockdown enhances autophagy and protects against ALI.；Therefore, TM9SF1‐mediated inhibition of autophagy in the LPS model may paradoxically exacerbate inflammation, which may be compatible with its function of promoting CLDN18 degradation in the lung injury context.Several limitations of this work should be acknowledged.
对本项目的价值
中高价值：属「营养感知—自噬—蛋白稳态轴」方向；mTOR / 自噬 / 蛋白质稳态栏目可用作本项目文献库与综述素材。 ｜ 价值分 3.0/5（★★★☆☆）
全文来源
PubMed PMC JATS（正文 35,340 字符，题名指纹 0.85，已过 PubMed PMCID 官方关联 + 题名指纹 + 正文长度归属校验）
原文题录
- 中文题名：TM9SF1 经增强 CLDN18 自噬降解促进 VILI 中肺泡上皮细胞 YAP 介导的 EMT
- 英文标题：TM9SF1 Promotes YAP-Mediated EMT of Alveolar Epithelial Cells in VILI by Enhancing Autophagic Degradation of CLDN18.
- 期刊与标识：Pulmonary circulation · PMID 42974107 · DOI 10.1002/pul2.70448 · PMC PMC13725937