Department of Blood Transfusion and Endocrinology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostic and Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao tong University School of Medicine, Shanghai 200011, China.
Aging (Albany NY). 2021 May 10;13(9):13087-13107. doi: 10.18632/aging.202991.
Mimecan encodes a secretory protein that is secreted into the human serum as two mature proteins with molecular masses of 25 and 12 kDa. We found 12-kDa mimecan to be a novel satiety hormone mediated by the upregulation of the expression of interleukin (IL)-1β and IL-6 in the hypothalamus. Mimecan was found to be expressed in human pituitary corticotroph cells and was up-regulated by glucocorticoids, while the secretion of adrenocorticotropic hormone (ACTH) in pituitary corticotroph AtT-20 cells was induced by mimecan. However, the effects of mimecan in adrenal tissue on the hypothalamic-pituitary-adrenal (HPA) axis functions remain unknown. We demonstrated that the expression of mimecan in adrenal tissues is significantly downregulated by hypoglycemia and scalded stress. It was down-regulated by ACTH, but upregulated by glucocorticoids through and studies. We further found that 12-kDa mimecan fused protein increased the corticosterone secretion of adrenal cells and . Interestingly, compared to litter-mate mice, the diurnal rhythm of corticosterone secretion was disrupted under basal conditions, and the response to restraint stress was stronger in mimecan knockout mice. These findings suggest that mimecan stimulates corticosterone secretion in the adrenal tissues under basal conditions; however, the down-regulated expression of mimecan by increased ACTH secretion after stress in adrenal tissues might play a role in maintaining the homeostasis of an organism's responses to stress.
Mimecan 编码一种分泌性蛋白，该蛋白分泌到人体血清中后会被加工为两种成熟蛋白，分子量分别为 25kDa 和 12kDa。我们发现 12kDa 的 mimecan 是一种新型的饱腹激素，其作用机制是在上调下丘脑白细胞介素（IL）-1β和 IL-6 的表达水平。Mimecan 被发现在人类垂体促皮质素细胞中表达，并可被糖皮质激素上调，而垂体促皮质素 AtT-20 细胞中促肾上腺皮质激素（ACTH）的分泌则可被 mimecan 诱导。然而，mimcan 在肾上腺组织中对下丘脑-垂体-肾上腺（HPA）轴功能的影响尚不清楚。我们证实，低血糖和烫伤应激会显著下调肾上腺组织中 mimecan 的表达。通过 和 研究发现，ACTH 可下调 mimecan 的表达，而糖皮质激素则可通过 和 途径上调 mimecan 的表达。我们进一步发现，12kDa 的 mimecan 融合蛋白可增加肾上腺细胞的皮质酮分泌。有趣的是，与同窝仔鼠相比，在基础状态下，mimcan 基因敲除鼠的皮质酮分泌昼夜节律被打乱，而在束缚应激下，其皮质酮分泌反应更强。这些发现提示，mimcan 可刺激基础状态下肾上腺组织中的皮质酮分泌；然而，应激后肾上腺组织中 ACTH 分泌增加导致的 mimecan 表达下调，可能在维持机体对应激反应的平衡中发挥作用。
