Anti-CLDN1 (C-terminal) polyclonal antibody

Claudin-1 is a recently discovered co-receptor for hepatitis C virus (HCV) that is required for late-stage binding of the virus. Because variants in the gene that encodes claudin-1 (CLDN1) could play a role in HCV infection, we conducted a 'whole gene association study' among injection drug users (IDUs) to examine whether CLDN1 genetic variants were associated with the risk of HCV infection or with viral clearance. In a cross sectional study, we examined genotype results for 50 single nucleotide polymorphisms (SNPs) across the CLDN1 gene region, comparing genotypes among participants with chronic HCV (n = 658) to those in IDUs who had cleared HCV (n = 199) or remained HCV-uninfected (n = 68). Analyses were controlled for racial ancestry (African-American or European-American) by stratification and logistic regression modeling. We found that participants who remained uninfected more often carried CLDN1 promoter region SNPs -15312C [odds ratio (OR), 1.72; 95% confidence interval (CI) 1.00-2.94; P = 0.048], -7153A (OR, 2.13; 95% CI, 1.25-3.62; P = 0.006) and -5414C (OR, 1.78; 95% CI, 1.06-3.00; P = 0.03). HCV-uninfected participants less often carried CLDN1 IVS1-2983C (OR, 0.55; 95% CI, 0.31-0.97; P = 0.04), which lies in intron 1. CLDN1 -15312C, -7153A and -5414C formed a haplotype in both the African-American and European-American participants and a haplotype analysis supported the association of CLDN1 -7153A in the HCV-uninfected participants. The analyses of HCV clearance revealed no associations with any SNP. These results indicate that genetic variants in regulatory regions of CLDN1 may alter susceptibility to HCV infection.

Background Atopic dermatitis (AD) is a common, chronic, severely pruritic, eczematous skin disease that seriously deteriorates the quality of life of patients. Scratching is a cardinal symptom of AD. Although the vicious itch-scratch cycle continues and aggravates skin barrier dysfunction in AD, how scratching induces skin barrier dysfunction through tight junctions remains unclear. Aim To study the effect of scratching on tight junctions in the itch-scratch cycle. Methods Scratching behaviour and skin barrier dysfunction on the neck and back in an AD mouse model were assessed. The expression of tight junction proteins was compared between the neck and back mice, and the mechanisms underlying the involvement of Akt/CLDN1 pathways in this process were explored. Results We used oxazolone to induce AD on the neck or back of mice. There was significantly more scratching behaviour and more pronounced skin barrier dysfunction with the neck than with the back. Downregulation of claudin-1 (CLDN1) and upregulation of Akt phosphorylation in skin were well correlated with scratching behaviour in this AD model. Furthermore, SC79, an agonist of Akt phosphorylation, could downregulate CLDN1 expression in HaCaT cells. An antagonist of Akt phosphorylation (LY294002) was used to treat the AD mice; this treatment rescued CLDN1 expression through inhibiting Akt phosphorylation in skin, and importantly, also inhibited the scratching behaviour induced by AD. Conclusion The results reveal the underlying mechanism of tight junction damage promoted by scratching in the itch-scratch cycle of AD, and opens a new avenue to pruritus management in AD, through Akt antagonists.