Secretion of soluble leptin receptors by exocrine and endocrine cells of the gastric mucosa
Secretion of soluble leptin receptors by exocrine and endocrine cells of the gastric mucosa
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DOI：
10.1152/ajpgi.00334.2005
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发表时间：
2006-02-01
影响因子：
4.5
通讯作者：
Bendayan, M
中科院分区：
文献类型：
--
作者：
Cammisotto, PG;Gingras, D;Bendayan, M
瘦素是由胃粘膜分泌到胃腔中的激素。它以其完整的形式存在于肠道中，在那里它调节营养吸收和肠粘膜完整性。我们已经确定了保护瘦素免受胃液恶劣条件影响的结合蛋白。免疫沉淀和蛋白质印迹分析表明，瘦素是存在于胃粘膜和胃液中，结合到对应于瘦素受体的细胞外结构域的蛋白质。在缺乏这种可溶性受体的情况下，瘦素迅速降解。大鼠胃粘膜上的免疫细胞化学鉴定了参与该复合物分泌的细胞和细胞内隔室。瘦素受体胞外区和瘦素沿着粗面内质网-高尔基体-颗粒的分泌途径存在，并在Chief和特定内分泌细胞的分泌颗粒中形成复合物。长型膜瘦素受体OB-Rb，蛋白酶激活剂弗林蛋白酶，和前蛋白转化酶7被发现在首席细胞颗粒，但不是在那些内分泌细胞。受体的脱落发生在未成熟的颗粒中。它的结论是，在未成熟的分泌颗粒的首席细胞，弗林蛋白酶激活前蛋白转化酶7，反过来，裂解的细胞外部分的膜结合的瘦素受体。瘦素与其可溶性受体结合形成一种复合物，这种复合物对胃液有抵抗力。另一方面，内分泌细胞通过与外分泌细胞不同的机制产生可溶性瘦素受体。
Leptin is a hormone secreted by the gastric mucosa into the lumen of the stomach. It is present in its intact form in the intestine where it regulates nutrient absorption and intestinal mucosa integrity. We have identified the binding protein that protects leptin from the harsh conditions of the gastric juice. Immunoprecipitations and Western blot analyses demonstrated that leptin is present in the gastric mucosa and the gastric juice, bound to a protein corresponding to the extracellular domain of the leptin receptor. In the absence of this soluble receptor, leptin is rapidly degraded. Immunocytochemistry on rat gastric mucosa identified the cells and intracellular compartments involved in secretion of this complex. Leptin receptor extracellular domain and leptin are present along the rough endoplasmic reticulum-Golgi-granules secretory pathways and form a complex in the secretory granules of Chief and specific endocrine cells. The long-form membrane leptin receptor OB-Rb, the protease activator furin, and proprotein convertase 7 were found in Chief cell granules but not in those of endocrine cells. The shedding of the receptor occurs in the immature granules. It is concluded that in the immature secretory granules of Chief cells, furin activates proprotein convertase 7 that, in turn, cleaves the extracellular portion of membrane-bound leptin receptors. Leptin bound to its soluble receptor forms a complex that is resistant to the gastric juice. Endocrine cells, on the other hand, generate a soluble leptin receptor by mechanisms different from those of the exocrine cells.