Luminal leptin activates mucin-secreting goblet cells in the large bowel
| Autor: | Annick Tsocas, Pascale Plaisancié, Olivier Thibaudeau, Robert Ducroc, André Bado, Mahmoud El Homsi, Sandra Guilmeau, Sandra Zoghbi |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Leptin
Male medicine.medical_specialty Colon Physiology Mucin 2 Biology Mice HT29 Cells Enteral Nutrition Physiology (medical) Internal medicine medicine Animals Humans Secretion Rats Wistar Cells Cultured Protein kinase C Leptin receptor Dose-Response Relationship Drug Hepatology digestive oral and skin physiology Mucin Mucins Gastroenterology respiratory system Mucus Rats Perfusion Endocrinology Goblet Cells |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 290:G805-G812 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00433.2005 |
| Popis: | Leptin has been suggested to be involved in tissue injury and/or mucosal defence mechanisms. Here, we studied the effects of leptin on colonic mucus secretion and rat mucin 2 (rMuc2) expression. Wistar rats and ob/ ob mice were used. Secretion of mucus was followed in vivo in the rat perfused colon model. Mucus secretion was quantified by ELISA, and rMuc2 mRNA levels were quantified by real-time RT PCR. The effects of leptin alone or in association with protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) inhibitors on mucin secreted by human mucus-secreting HT29-MTX cells were determined. Leptin was detected in the rat colonic lumen at substantial levels. Luminal perfusion of leptin stimulates mucus-secreting goblet cells in a dose-dependent manner in vivo in the rat. Leptin (10 nmol/l) increased mucus secretion by a factor of 3.5 and doubled rMuc2 mRNA levels in the colonic mucosa. There was no damage to mucosa 24 h after leptin, but the number of stained mucus cells significantly increased. Leptin-deficient ob/ ob mice have abnormally dense mucus-filled goblet cells. In human colonic goblet-like HT29-MTX cells expressing leptin receptors, leptin increased mucin secretion by activating PKC- and PI3K-dependent pathways. This is the first demonstration that leptin, acting from the luminal side, controls the function of mucus-secreting goblet cells. Because the gel layer formed by mucus at the surface of the intestinal epithelium has a barrier function, our data may be relevant physiologically in defence mechanisms of the gastrointestinal tract. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|