Antoniewicz Jakub, Nedoszytko Bogusław, Lange Magdalena, Wierzbicka Justyna, Górska-Ponikowska Magdalena, Niedoszytko Marek, Zabłotna Monika, Nowicki Roman J, Żmijewski Michał A
Department of Histology, Medical University of Gdansk, Gdansk, Poland.
Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland.
Postepy Dermatol Alergol. 2021 Jun;38(3):461-472. doi: 10.5114/ada.2021.107933. Epub 2021 Jul 26.
Mastocytosis is a rare disease characterized by abnormal growth and accumulation of tissue mast cells (MC) in one or more organ systems and is classified as being either cutaneous mastocytosis (CM) or systemic mastocytosis (SM). In the pioneer studies of Slominski's group, a fully functional hypothalamic-pituitary-adrenal axis equivalent has been discovered in various tissues, including skin.
In the present study we investigated potential involvement of hypothalamus-pituitary-adrenal (HPA) cutaneous equivalent in ongoing mastocytosis.
The expression of HPA elements: CRH, UCN1, UCN2, UCN3, CRHR1, POMC, MC1R, MC2R and NR3C1 was assessed for their mRNA level in skin biopsies of adult patients with mastocytosis and healthy donors (n = 16 and 19, respectively), while CRH, UCN1, CRHR1, ACTH and MC1R were selected for immunostaining assay (n = 13 and 7, respectively). The expression of CRH receptor 1 (CRHR1) isomers was investigated by RT-PCR. The ELISA was used for detection of cortisol, CRH, UCN and ACTH in the serum.
The decrease in the expression of HPA element of skin equivalent was observed on both mRNA and protein levels, however quantification of immunohistochemical data was impeded due to melanin in epidermis. Furthermore, observed infiltration of dermis with HPA elements overexpressing mononuclear cells, which is in the agreement with an study showing a high expression of HPA elements by mast cells.
Taken together, it was confirmed that the expression elements of HPA was modulated in mastocytosis, thus the potential involvement of general and local stress responses in its pathogenesis should be postulated and further investigated.
肥大细胞增多症是一种罕见疾病，其特征为一个或多个器官系统中组织肥大细胞（MC）异常生长和积聚，可分为皮肤肥大细胞增多症（CM）或系统性肥大细胞增多症（SM）。在斯洛明斯基小组的开创性研究中，已在包括皮肤在内的各种组织中发现了功能完备的下丘脑 - 垂体 - 肾上腺轴等效物。
在本研究中，我们调查了下丘脑 - 垂体 - 肾上腺（HPA）皮肤等效物在进行性肥大细胞增多症中的潜在参与情况。
评估了HPA元件（促肾上腺皮质激素释放激素（CRH）、促肾上腺皮质激素释放激素1型（CRHR1）、阿黑皮素原（POMC）、黑皮质素受体1型（MC1R）、黑皮质素受体2型（MC2R）和核受体亚家族3C成员1（NR3C1））在成年肥大细胞增多症患者和健康供体（分别为n = 16和19）皮肤活检组织中的mRNA水平，同时选择CRH、促肾上腺皮质激素释放激素1型（CRHR1）、促肾上腺皮质激素（ACTH）和黑皮质素受体1型（MC1R）进行免疫染色分析（分别为n = 13和7）。通过逆转录 - 聚合酶链反应（RT - PCR）研究CRH受体1型（CRHR1）异构体的表达。采用酶联免疫吸附测定（ELISA）检测血清中的皮质醇、CRH、促肾上腺皮质激素释放激素（UCN）和促肾上腺皮质激素（ACTH）。
在mRNA和蛋白质水平均观察到皮肤等效物的HPA元件表达降低，但由于表皮中的黑色素阻碍了免疫组织化学数据的定量分析。此外，观察到真皮中有过表达HPA元件的单核细胞浸润，这与一项显示肥大细胞高表达HPA元件的研究结果一致。
综上所述，证实了HPA的表达元件在肥大细胞增多症中受到调节，因此应推测并进一步研究全身和局部应激反应在其发病机制中的潜在参与情况。
