Cldn3, short for claudin-3, is a transmembrane protein that is a crucial component of tight junctions in cell-cell adhesion. Tight junctions play a vital role in maintaining the integrity of epithelial and endothelial barriers, and Cldn3 is involved in regulating paracellular permeability. It may also be associated with multiple signaling pathways, though the exact ones are still being elucidated. Understanding its function can be facilitated through genetic models such as gene knockout (KO) or conditional knockout (CKO) mouse models for in-vivo studies [1,6].

In pregnancy-induced hypertension, the mRNA expression levels of Cldn3 were significantly reduced in placental tissues and peripheral blood samples. Overexpression of Cldn3 in human trophoblast HTR8/SVneo cells increased cell proliferation, invasion, and migration while reducing apoptosis, potentially through upregulating matrix metalloproteinase (MMP) expression via the ERK1/2 signaling pathway [1].

In cholangiocarcinoma, TET1 promotes Cldn3 transcription by targeting its promoter region for demethylation, and PPM1G can impede CCA progression by catalyzing TET1 dephosphorylation, thus impairing Cldn3 promoter demethylation [2].

In hepatocellular carcinoma (HCC), Cldn3 down-regulation was observed in most primary HCCs, correlating with shorter patient survival. Ectopic expression of Cldn3 in HCC cells inhibited cell motility, invasiveness, and tumor formation in nude mice by inactivating the Wnt/β-catenin-epithelial mesenchymal transition (EMT) axis [3].

In ovarian cancer, Cldn3 is positively correlated with cancer progression, and its S-palmitoylation on three juxtamembrane cysteine residues contributes to accurate plasma membrane localization and protein stability, promoting tumorigenesis [4].

In pancreatic cancer, the DPP10-AS1/miR-324-3p/Cldn3 axis was identified, where DPP10-AS1 sequesters miR-324-3p to release Cldn3 expression, promoting PC malignancy [5].

In colitis, loss of Cldn3 expression in mouse models promoted colitis by altering gut microbiota, which could modulate fatty acid metabolism and oxidative stress response [6].

In conclusion, Cldn3 plays essential roles in maintaining cell-cell adhesion and barrier function. Through model-based research, it has been shown to be involved in various disease conditions such as pregnancy-induced hypertension, cholangiocarcinoma, HCC, ovarian cancer, pancreatic cancer, and colitis. These findings highlight the importance of Cldn3 in disease development and suggest its potential as a therapeutic target in these disease areas.