Insulin receptor signaling engages bladder urothelial defenses that limit urinary tract infection.
Cell Rep
; 43(4): 114007, 2024 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-38517889
ABSTRACT
Urinary tract infections (UTIs) commonly afflict people with diabetes. To better understand the mechanisms that predispose diabetics to UTIs, we employ diabetic mouse models and altered insulin signaling to show that insulin receptor (IR) shapes UTI defenses. Our findings are validated in human biosamples. We report that diabetic mice have suppressed IR expression and are more susceptible to UTIs caused by uropathogenic Escherichia coli (UPEC). Systemic IR inhibition increases UPEC susceptibility, while IR activation reduces UTIs. Localized IR deletion in bladder urothelium promotes UTI by increasing barrier permeability and suppressing antimicrobial peptides. Mechanistically, IR deletion reduces nuclear factor κB (NF-κB)-dependent programming that co-regulates urothelial tight junction integrity and antimicrobial peptides. Exfoliated urothelial cells or urine samples from diabetic youths show suppressed expression of IR, barrier genes, and antimicrobial peptides. These observations demonstrate that urothelial insulin signaling has a role in UTI prevention and link IR to urothelial barrier maintenance and antimicrobial peptide expression.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Infecções Urinárias
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Bexiga Urinária
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Receptor de Insulina
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Transdução de Sinais
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Urotélio
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article