Luminal leptin activates mucin-secreting goblet cells in the large bowel.
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.
Plaisancie
Pascale
P
INSERM, U773, Centre de Recherche Bichat Beaujon CRB3, Paris, France.
Ducroc
Robert
R
El Homsi
Mahmoud
M
Tsocas
Annick
A
Guilmeau
Sandra
S
Zoghbi
Sandra
S
Thibaudeau
Olivier
O
Bado
Andre
A
D000818:Animals; D002478:Cells, Cultured; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004750:Enteral Nutrition; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D020738:Leptin / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D009077:Mucins / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D020738:Leptin; D009077:Mucins