Luminal leptin activates mucin-secreting goblet cells in the large bowel
Luminal leptin activates mucin-secreting goblet cells in the large bowel
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DOI：
10.1152/ajpgi.00433.2005
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发表时间：
2006-04-01
影响因子：
4.5
通讯作者：
Bado, A
中科院分区：
文献类型：
--
作者：
Plaisancie, P;Ducroc, R;Bado, A
腔内瘦素激活大肠中分泌粘蛋白的杯状细胞。Am J Physiol Gasterintest liver Physiol290：G805-G812,2006年；DOI：10.1152/ajpgi.00433.2005。-瘦素被认为参与了组织损伤和/或粘膜防御机制。在此，我们研究了瘦素对结肠粘液分泌和大鼠粘蛋白2(RMuc2)表达的影响。实验采用Wistar大鼠和ob/ob小鼠。在大鼠灌流结肠模型中观察粘液的分泌情况。用ELISA法测定粘液分泌量，用实时荧光定量RT-PCR法测定rMuc2mRNA水平。检测瘦素单独或与蛋白激酶C(PKC)和磷脂酰肌醇3-激酶(PI3K)抑制剂联合应用对分泌粘液的HT29-MTX细胞分泌粘蛋白的影响。在大鼠的结肠腔中检测到大量的瘦素。体内灌流瘦素以剂量依赖的方式刺激粘液分泌的杯状细胞。瘦素(10nmol/L)使结肠粘膜粘液分泌量增加3.5倍，并使rMuc2基因表达水平增加一倍。瘦素作用24 h后，粘膜未见损伤，但染色的粘液细胞明显增多。瘦素缺乏的ob/ob小鼠有异常致密的粘液填充的杯状细胞。在表达瘦素受体的人结肠杯样HT29-MTX细胞中，瘦素通过激活PKC和PI3K依赖的途径增加粘蛋白的分泌。这是瘦素从管腔一侧起作用，控制分泌粘液的杯状细胞功能的第一次证明。由于粘液在肠上皮表面形成的凝胶层具有屏障功能，我们的数据可能与胃肠道防御机制的生理学相关。
Luminal leptin activates mucin-secreting goblet cells in the large bowel. Am J Physiol Gastrointest Liver Physiol 290: G805-G812, 2006; doi:10.1152/ajpgi.00433.2005.-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.