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Role of TRPV1 receptor in inflammation and impairment of esophageal mucosal integrity in a murine model of nonerosive reflux disease

Silva, R. O. ; Bingana, R. D. ; Sales, T. M. A. L. ; Moreira, R. L. R. ; Costa, D. V. S. ; Sales, K. M. O. ; Brito, G. A. C. ; Santos, A. A. ; Souza, M. Â. N. ; Soares, P. M. G. ; Sifrim, D. ; Souza, M. H. L. P.

Neurogastroenterology and motility, 2018-08, Vol.30 (8), p.e13340-n/a [Periódico revisado por pares]

England: Wiley Subscription Services, Inc

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  • Título:
    Role of TRPV1 receptor in inflammation and impairment of esophageal mucosal integrity in a murine model of nonerosive reflux disease
  • Autor: Silva, R. O. ; Bingana, R. D. ; Sales, T. M. A. L. ; Moreira, R. L. R. ; Costa, D. V. S. ; Sales, K. M. O. ; Brito, G. A. C. ; Santos, A. A. ; Souza, M. Â. N. ; Soares, P. M. G. ; Sifrim, D. ; Souza, M. H. L. P.
  • Assuntos: Animal models ; Antagonists ; Capsaicin receptors ; Capsazepine ; Esophagus ; Fluorescein ; Inflammation ; Mucosa ; mucosal integrity ; Mucous membrane ; non‐erosive reflux disease ; Pepsin ; Permeability ; Peroxidase ; Resiniferatoxin ; Rodents ; Stomach ; Surgery ; Taurodeoxycholic acid ; Transient receptor potential proteins ; TRPV1 ; Ulcers ; Western blotting
  • É parte de: Neurogastroenterology and motility, 2018-08, Vol.30 (8), p.e13340-n/a
  • Notas: Funding information
    This work was supported by National Council of Technological and Scientific Development (CNPq, Brazil), grant number 400752/2013‐1.
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  • Descrição: Background Microscopic inflammation and impairment of the esophageal epithelial barrier are considered relevant for perception of symptoms in patients with nonerosive reflux disease (NERD). In these patients, the receptor transient receptor potential vanilloid 1 (TRPV1) is overexpressed in the esophageal mucosa, but its role is not yet fully understood. We evaluated the role of TRPV1 in esophageal inflammation and mucosal barrier impairment in a murine model of NERD. Methods Nonerosive reflux disease was surgically induced in Swiss mice by pyloric substenosis and ligature of the gastric fundus, and the mice were killed 7 days post surgery. The experimental groups were: I, sham surgery (negative control); II, NERD untreated; III and IV, NERD + SB366791 or capsazepine (TRPV1 antagonists); and V, NERD + resiniferatoxin (for long‐term desensitization of TRPV1). The esophagus was collected for western blotting and histopathology and for evaluation of wet weight, myeloperoxidase (MPO), keratinocyte‐derived chemokine (KC), transepithelial electrical resistance (TEER), and basal permeability to fluorescein. Key Results Compared to sham, NERD mice had increased esophageal wet weight and MPO and KC levels. The mucosa had no ulcers but exhibited inflammation. NERD mice showed mucosal TRPV1 overexpression, a more pronounced decrease in TEER at pH 0.5 (containing pepsin and taurodeoxycholic acid), and increased basal permeability. Pharmacological modulation of TRPV1 prevented esophageal inflammation development, TEER changes by acidic exposure, and increase in esophageal permeability. Conclusions & Inferences The TRPV1 receptor has a critical role in esophageal inflammation and mucosal barrier impairment in NERD mice, suggesting that TRPV1 might be a pharmacological target in patients with NERD. The TRPV1 receptor has a critical role in esophageal inflammation and mucosal barrier impairment in NERD mice, suggesting that TRPV1 might be a pharmacological target in patients with NERD.
  • Editor: England: Wiley Subscription Services, Inc
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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