Research Paper Volume 13, Issue 9 pp 13087—13107
The expression of mimecan in adrenal tissue plays a role in an organism’s responses to stress
- 1 Department of Blood Transfusion and Endocrinology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
- 2 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
- 3 Department of Endocrine Metabolism, Minhang Hospital, Fudan University, Shanghai 201199, China
- 4 Department of Respiration, Yangpu Hospital, Tongji University, Shanghai 200090, China
- 5 Department of Endocrinology and Metabolism, Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei 230001, Anhui, China
- 6 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Received: January 19, 2021 Accepted: April 2, 2021 Published: May 10, 2021https://doi.org/10.18632/aging.202991
How to Cite
Copyright: © 2021 Su et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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 in vivo and in vitro studies. We further found that 12-kDa mimecan fused protein increased the corticosterone secretion of adrenal cells in vivo and in vitro. 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.