Claudin 18 (CLDN18) is a tight junction protein that is highly expressed in the lung. While mice lacking CLDN18 exhibit the expected loss of epithelial integrity in the lung, these animals also have unexpectedly large lungs. In this issue of the JCI, Zhou, Flodby, and colleagues reveal that the increased lung size of Cldn18–/– mice is the result of increased type 2 alveolar epithelial (AT2) cell proliferation. This increase in proliferation was shown to be driven by translocation of the transcriptional regulator Yes-associated protein (YAP) to the nucleus and subsequent induction of proliferative pathways. CLDN18-deficent mice also had increased frequency of lung adenocarcinomas. Together, the results of this study advance our understanding of the mechanisms that likely regulate homeostasis of the normal lung as well as promote the proliferative state of malignant cells found in lung adenocarcinomas thought to originate from AT2 cells.

Claudin 18（CLDN18）是在肺中高表达的紧密连接蛋白。虽然缺少CLDN18的小鼠在肺部表现出预期的上皮完整性丧失，但这些动物的肺部也出乎意料地大。在本期JCI中，Zhou，Flodby及其同事发现，Cldn18 – / –小鼠的肺部大小增加是2型肺泡上皮（AT2）细胞增殖增加的结果。增殖的增加被证明是由转录调节因子Yes相关蛋白（YAP）易位至细胞核和随后的增殖途径诱导而引起的。缺乏CLDN18的小鼠的肺腺癌发生率也增加。一起，