Disease relevance of Cldn4

• Overexpression of claudin-3 and claudin-4 receptors in uterine serous papillary carcinoma: novel targets for a type-specific therapy using Clostridium perfringens enterotoxin (CPE) [1].
• CONCLUSIONS.: Claudin-3 and claudin-4 receptors may offer promising targets for the use of CPE as a novel type-specific therapy against this highly aggressive and chemotherapy-resistant variant of endometrial cancer [1].
• Finally, the in vivo therapeutic effect of sublethal doses of CPE was studied in SCID mouse xenografts harboring subcutaneous and intraperitoneal USPC that expressed claudin-3 and claudin-4 [1].
• Helicobacter pylori activates myosin light-chain kinase to disrupt claudin-4 and claudin-5 and increase epithelial permeability [2].

High impact information on Cldn4

• Clostridium perfringens enterotoxin (CPE), a single approximately 35-kD polypeptide, was reported to specifically bind to claudin-3/RVP1 and claudin-4/CPE-R at its COOH-terminal half [3].
• In conclusion, disruptions of the tight junctions observed in this study implicate host cell signaling pathways, including the phosphorylation of myosin light chain and the regulation of tight-junctional proteins claudin-4 and claudin-5, in the pathogenesis of H. pylori infection [2].
• H. pylori strain SS1 was able to directly increase paracellular permeability, in the absence of host inflammatory cells, by disrupting the tight-junctional proteins occludin, claudin-4, and claudin-5 in confluent nontransformed epithelial cells [2].
• Conversely, in LLC-PK1 cells, claudin-2 and -15 increased the permeability for Na+, whereas claudin-4 and -11 were without effect [4].
• Expression of claudin-4 increased TER in both cell lines, whereas effects of the others on TER were variable [4].

Biological context of Cldn4

• Using gene expression profiling, we recently identified high expression of the claudin-3 and claudin-4 receptors in a limited set of USPC [1].
• Our results indicate that claudin-4, -8, and -12 are expressed in umbrella cells, where they may impart the high-resistance phenotype associated with this cell type, and that in some instances tight junction proteins are also associated at the sites of cell contact of the underlying cell layers, perhaps playing some role in cell-cell adhesion [5].

Anatomical context of Cldn4

• Characteristics of claudin expression in follicle-associated epithelium of Peyer's patches: preferential localization of claudin-4 at the apex of the dome region [6].
• Particularly, distribution of claudin-4 in the TAL and distal convoluted tubules was characteristic of bovine nephrons as were differences in the expression patterns of claudins 2 and 3 [7].

Associations of Cldn4 with chemical compounds

• METHODS.: Claudin-3 and claudin-4 receptor expression was analyzed at the mRNA and protein levels in flash-frozen and formalin-fixed, paraffin-embedded tissue from 20 consecutive USPC patients [1].

Analytical, diagnostic and therapeutic context of Cldn4

• Membranous immunoreactivity for claudin-4 protein expression was documented in the majority of USPC specimens tested by immunohistochemistry, whereas only a low level of membranous staining was found in normal endometrial control tissue samples [1].

References