# Diabetes compromises tight junction protein claudin 14 in the urinary bladder

## TL;DR

Diabetes weakens a key bladder protein (claudin 14), which may increase infection risk, and calcium levels may help restore it.

## Contribution

This study is the first to show that high glucose in diabetes reduces claudin 14 in bladder cells, and calcium can help restore it.

## Key findings

- Diabetes reduces claudin 14 expression in human bladder cells and mouse models.
- High glucose lowers intracellular calcium, which correlates with reduced claudin 14.
- Calcium supplementation restores claudin 14 and improves cell migration in high glucose conditions.

## Abstract

Infections are common in patients with diabetes. Moreover, increasing incidence of antibiotic resistance impedes the complete bacterial clearance and calls for alternative treatment strategies. Along with antibacterial resistance, compromised host conditions create a favorable condition for the disease progression. In particular, cell junction proteins are of major importance as they contribute to a tight cell barrier, protecting against invading pathogens. However, the impact of high glucose on cell junction proteins has received little attention in the urinary bladder but merits closer investigation. Here, we report that during diabetes the expression of cell junction protein, claudin 14 is compromised in the human urine exfoliated cells and in the urinary bladder of type 2 diabetic mouse. Further in vitro analysis confirmed a direct correlation of lower intracellular calcium levels with claudin 14 expression in high glucose-treated human uroepithelial cells. Moreover, external calcium supplementation in high glucose-treated cells significantly affected the cell migration and restored the claudin 14 expression through focal adhesion and β-1 integrins. Strengthening the epithelial barrier is essential, especially in individuals with diabetes where basal calcium levels could contribute.

The online version contains supplementary material available at 10.1007/s00441-024-03908-4.