Cldn1, encoding the transmembrane protein claudin-1, is critical for the formation of tight junctions (TJ) in the epidermal barrier structure. Tight junctions play a vital role in maintaining the permeability and integrity of the normal epithelial cell barrier [2,5].

In preeclampsia, Cldn1 is significantly downregulated in chorionic villi samples. Knockdown of Cldn1 in HTR-8/SVneo cells inhibits cell proliferation and induces apoptosis, while overexpression reverses these effects. The gene BIRC3 is potentially downstream of Cldn1 and involved in apoptosis regulation. Decreased Cldn1 inhibits BIRC3 expression and increases cleaved PARP levels, participating in preeclampsia pathogenesis [1]. In early-onset preeclampsia, downregulation of Cldn1 impairs trophoblast invasion and endovascular trophoblast differentiation [4].

In airway smooth muscle cells (ASMCs) related to asthma, Cldn1 is upregulated by platelet-derived growth factor BB (PDGF-BB). Knockdown of Cldn1 inhibits ASMCs proliferation, migration, invasion, and inflammation, while overexpression promotes these processes. Cldn1 directly interacts with matrix metalloproteinase 14 (MMP14) and positively regulates its expression [3].

In keratinocytes, knockout of Cldn1 leads to reduced barrier function, decreased expression of barrier-related genes, and abnormal epidermal stratification [2].

In conclusion, Cldn1 is essential for maintaining the integrity of epithelial barriers and plays a significant role in multiple physiological and pathological processes. Studies using gene knockout models, such as in preeclampsia, asthma, and skin-related disorders, have revealed its functions in cell proliferation, apoptosis, invasion, and barrier formation, providing insights into the mechanisms of these diseases.