Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation
| Autor: | Ignazio Castagliuolo, Anna-Lisa Stefani, Elisa Beggiao, Paola Brun, Cristina Mastrotto, Giorgio Palù, Giacomo Carlo Sturniolo, Luisa Barzon |
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| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Physiology Neuropeptide Inflammation Biology Severity of Illness Index Cell Line chemistry.chemical_compound Mice Immune system Physiology (medical) Internal medicine medicine Animals Humans Receptors Neurotensin RNA Messenger Colitis Intestinal Mucosa Receptor Neurotensin Mice Inbred BALB C Wound Healing Hepatology Dextran Sulfate Gastroenterology medicine.disease Inflammatory Bowel Diseases Epithelium Intestines medicine.anatomical_structure Endocrinology chemistry Case-Control Studies Chronic Disease Quinolines Pyrazoles Colitis Ulcerative medicine.symptom Wound healing |
| Zdroj: | American journal of physiology. Gastrointestinal and liver physiology. 288(4) |
| ISSN: | 0193-1857 |
| Popis: | Because neurotensin (NT) and its high-affinity receptor (NTR1) modulate immune responses, chloride secretion, and epithelial cell proliferation, we sought to investigate their role in the repair process that follows the development of mucosal injuries during a persistent inflammation. Colonic NT and NTR1, mRNA, and protein significantly increased only after dextran sodium sulfate (DSS)-induced inflammatory damage developed. Colitis-induced body weight loss, colonic myeloperoxidase activity, and histological damage were significantly enhanced by SR-48642 administration, a nonpeptide NTR1 antagonist, whereas continuous NT infusion ameliorated colitis outcome. To evaluate the NT and NTR1 role in tissue healing, mucosal inflammatory injury was established administering 3% DSS for 5 days. After DSS discontinuation, mice rapidly gained weight, ulcers were healed, and colonic NT, NTR1, and cyclooxygenase (COX)-2 mRNA levels were upregulated, whereas SR-48642 treatment caused a further body weight loss, ulcer enlargement, and a blunted colonic COX-2 mRNA upregulation. In a wound-healing model in vitro, NT-induced cell migration in the denuded area was inhibited by indomethacin but not by an antitransforming growth factor-β neutralizing antibody. Furthermore, NT significantly increased COX-2 mRNA levels by 2.4-fold and stimulated PGE2release in HT-29 cells. These findings suggest that NT and NTR1 are part of the network activated after mucosal injuries and that NT stimulates epithelial restitution at least, in part, through a COX-2 dependent pathway. |
| Databáze: | OpenAIRE |
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