CLDN2

What is CLDN2 protein?

CLDN2 gene (claudin 2) is a protein coding gene which situated on the short arm of chromosome X at locus Xq22. This gene product belongs to the claudin protein family whose members have been identified as major integral membrane proteins localized exclusively at tight junctions. Claudins are expressed in an organ-specific manner and regulate tissue-specific physiologic properties of tight junctions. This protein is expressed in the intestine. The CLDN2 protein is consisted of 230 amino acids and CLDN2 molecular weight is approximately 24.5 kDa.

What is the function of CLDN2 protein?

The CLDN2 protein is a critical component of the tight junctions in epithelial and endothelial cells. It forms paracellular channels that are selective for cations and water, contributing to the permeability of the epithelial barrier. Claudin-2 plays a significant role in the intestines, particularly in the proximal tubules of the kidneys and the gut, where it aids in the energy-efficient transport of ions and water. It is also implicated in various diseases, including cancer, inflammation, and fibrosis, and its expression levels can be correlated with disease progression. Furthermore, Claudin-2 has been identified as a potential biomarker for conditions like colorectal cancer and is targeted by vitamin D receptor signaling, which suggests its involvement in cellular processes beyond its known effects on tight junction function.

Fig1. Claudin-2 structure and interactions with cytosolic multidomain adapters. (Shruthi Venugopal, 2019)

CLDN2 related signaling pathway

The CLDN2 protein, a component of tight junctions, forms paracellular channels that are selectively permeable to cations and water, influencing the epithelial barrier's permeability. It plays a crucial role in ion and water transport in the kidneys and gut. Beyond its structural function, CLDN2 is implicated in cellular processes such as proliferation, migration, and cell fate determination, which are relevant to diseases like cancer, inflammation, and fibrosis. Dysregulation of CLDN2 is associated with various pathologies, and signaling pathways that are overactivated in diseases can alter CLDN2 expression. For instance, in colorectal cancer, CLDN2 has been shown to promote tumor growth and metastasis by suppressing the transcription of NDRG1, a metastasis suppressor gene, and is being explored as a potential biomarker for cancer detection and prognosis.

CLDN2 related diseases

CLDN2 is associated with several diseases, particularly inflammatory bowel disease (IBD), where its expression is elevated in inflamed gut tissue. This dysregulation contributes to increased intestinal permeability and may play a role in the pathogenesis of IBD. Additionally, CLDN2 has been implicated in cancer, particularly colorectal cancer, where it promotes tumor growth and metastasis. Recent studies suggest that CLDN2 may also serve as a biomarker for pre-diabetes, with elevated levels observed in patients with impaired glucose tolerance and type 2 diabetes. Its expression is influenced by various inflammatory cytokines, indicating its potential role in metabolic disorders and inflammation-related diseases.

Bioapplications of CLDN2

CLDN2 has bioapplications in various medical fields, primarily serving as a tight junction protein crucial for paracellular transport of ions and water in leaky epithelia. It is notably implicated in the progression of inflammatory bowel disease due to its role in intestinal barrier function. Furthermore, CLDN2's expression is elevated in several cancers, including colorectal, where it promotes tumor growth and metastasis, suggesting its potential as a therapeutic target. Additionally, CLDN2 has emerged as a promising biomarker for early diagnosis of pre-diabetes, with its expression significantly upregulated in both diabetic mice models and human patients with impaired glucose tolerance and type 2 diabetes. These applications underscore CLDN2's significance in disease diagnosis, prognosis, and treatment strategies.

Case Study 1: Mingtian Wei, 2021

In colorectal cancer (CRC), Claudin-2 (CLDN2) is linked to tumor progression and poor survival rates. This research shows that reducing CLDN2 expression enhances NDRG1 transcription, thereby inhibiting CRC growth and spread. This effect is due to the disruption of the CLDN2/ZO1/ZONAB complex, allowing ZONAB to enter the nucleus and activate NDRG1. This finding points to a new CLDN2/ZO1/ZONAB-NDRG1 pathway in CRC and positions CLDN2 as a potential therapeutic target.

Fig1. Representative band of CLDN2 levels in CRC cell lines by western blot analysis.

Fig2. The interaction and correlation between ZONAB and ZO1/NDRG1/CLDN2 in HT29 cells knocking out CLDN2.

Case Study 2: Yang Songtao, 2024

Pre-diabetes, a precursor to diabetes, represents a critical metabolic state that allows for early intervention. Identifying this condition early is vital for preventing diabetes, making the search for accurate biomarkers essential. Researchers analyzed gene expression in clinical samples across non-diabetic, impaired glucose tolerance, and type 2 diabetes groups using the GSE164416 dataset and confirmed our findings in mice models with high-fat diets and STZ-induced diabetes. The analysis revealed shared differentially expressed genes (Co-DEGs) in impaired glucose tolerance and type 2 diabetes, with CLDN2 being a standout.

Fig3. Western blot showing the overexpression of CLDN2 in both HFD and STZ mice.

Fig4. Correlation of CLDN2 level with clinical parameters.

CLDN2 has several biochemical functions, for example, identical protein binding,protein binding,structural molecule activity. Some of the functions are cooperated with other proteins, some of the functions could acted by CLDN2 itself. We selected most functions CLDN2 had, and list some proteins which have the same functions with CLDN2. You can find most of the proteins on our site.

CLDN2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with CLDN2 here. Most of them are supplied by our site. Hope this information will be useful for your research of CLDN2.

KRT31;NOTCH2NL;KRTAP4-12;TJP1