Claudin-12 sustains urothelial barrier defense against uropathogenic E. coli via calcium-dependent immunomodulation.

Authors

Yanpeng Tian, Hongping Tong, Yinhui Sun, Longcheng Hong, Xiaoming Lei, Feng Wang

Published in

iScience. Volume 29. Issue 9. Pages 117190. Sep 18, 2026. Epub Aug 22, 2026.

Abstract

Urothelial barrier compromise defines inflammatory cystitis, though molecular regulators remain elusive. We identify claudin-12-a bladder-enriched tight junction protein-as an essential barrier component against uropathogenic E. coli (UPEC) invasion. At 72 h post-infection in the murine model of UPEC-induced cystitis, infection triggered dysregulation of canonical tight junction components (claudin-12, ZO-1, occludin), with claudin-12 exhibiting maximal depletion. Immunofluorescence confirmed profound tight junction disassembly in infected bladders. Consistent with this structural defect, claudin-12-knockout mice developed exacerbated acute cystitis, manifesting elevated bacterial colonization, neutrophil/monocyte infiltration, pro-inflammatory gene upregulation, and epithelial denudation. Mechanistically, claudin-12 loss increased calcium permeability in urothelial cells during UPEC infection, driving intracellular calcium accumulation and subsequent activation of apoptosis-related pathways. Notably, pharmacological inhibition of calcium accumulation by TMB-8 reversed both UPEC-induced apoptosis and claudin-12 depletion. Thus, claudin-12 emerges as a pivotal orchestrator of urothelial defense, wherein its regulation of calcium flux restrains UPEC-driven inflammation-revealing therapeutic potential for barrier-repair strategies.

PMID:
42668535
Bibliographic data and abstract were imported from PubMed on 30 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.