Role of TRPV1 receptor in inflammation and impairment of esophageal mucosal integrity in a murine model of nonerosive reflux disease
| Autor: | Daniel Sifrim, Armênio Aguiar dos Santos, Kamila Maria Oliveira Sales, Pedro Marcos Gomes Soares, Gerly Anne de Castro Brito, Renan O. Silva, Marcellus H.L.P. Souza, Miguel Ângelo Nobre e Souza, Deiziane Viana da Silva Costa, Thiago M. Sales, Rhubens Levy R. Moreira, Rudy D. Bingana |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology Nerd Resiniferatoxin TRPV1 Inflammation Gastroenterology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pepsin Internal medicine medicine Esophagus biology Endocrine and Autonomic Systems business.industry 030104 developmental biology medicine.anatomical_structure chemistry Myeloperoxidase biology.protein 030211 gastroenterology & hepatology Taurodeoxycholic acid medicine.symptom business |
| Zdroj: | Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. |
| ISSN: | 1365-2982 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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