MiR-223通过调控组胺N-甲基转移酶（HNMT）参与特应性皮炎病理过程的作用机制研究

Atopic dermatitis (AD) is a complex allergic skin disease, which is characterized by typically distributed eczematous skin lesions and intense pruritus. MiR-223 is a hematopoietic specific microRNA with crucial functions in the development of myeloid lineage cells such as granulocytes, monocytes and mast cells. In our previous study, we found that the levels of miR-223 were significantly increased in the sera, peripheral blood cells and skin tissues of the patients with AD. We also identified histamine N-methyltransferase (HNMT) as one of the targets of miR-223. HNMT is one of the two enzymes involved in the metabolism of histamine, and is associated with the pathogenesis of some allergic diseases such as asthma and AD. However, the role of miR-223 in AD needs to be further clarified, and the molecular mechanisms of miR-223 in the pathogenesis of AD remain unclear. In the present study, we will extensively investigate the role of miR-223 in the pathogenesis of AD at the molecular level, cell level and animal level. NC/Nga mice will be used as spontaneous AD model, and miR-223 knockout mice and HNMT knockout mice will be used to establish induced AD model. Moreover, adenovirus system will be used to overexpress miR-223 or HNMT, or knockdown HNMT, in the peripheral blood cells and bone marrow cells of the mice. Overall, we aim to elucidate the pathogenic pathway of "miR-223 - HNMT - histamine metabolism - AD", and provide additional insights towards the clinical treatment of AD.

特应性皮炎是一种病因复杂的炎症性皮肤病。MiR-223在粒细胞、单核细胞、肥大细胞等骨髓来源细胞的系统发育中起着重要作用。在本课题组的前期研究中，发现miR-223在特应性皮炎患者的血清、血细胞及皮肤组织中均显著升高，并且验证了组胺N-甲基转移酶（HNMT）是miR-223的靶点之一。但是，miR-223在特应性皮炎中的作用仍需进一步验证，其参与特应性皮炎病理过程的具体机制也尚未明确。因此，本项目拟在前期研究的基础上，以NC/Nga小鼠、miR-223基因敲除小鼠、HNMT基因敲除小鼠作为主要模型，并通过腺病毒在小鼠血液细胞及骨髓细胞中进行相关基因的过表达或敲减，从分子生物学、细胞和整体动物水平探讨miR-223通过调控HNMT的表达而参与特应性皮炎病理过程的具体作用机制。本项目旨在阐明"miR-223-HNMT-组胺代谢-特应性皮炎"这一致病途径，并为临床治疗特应性皮炎提供新的理论依据。

本项目在前期研究的基础上，以NC/Nga小鼠、miR-223基因敲除小鼠、HNMT基因敲除小鼠作为主要模型，并通过腺病毒在小鼠血液细胞及骨髓细胞中进行相关基因的过表达或敲减，从分子生物学、细胞和整体动物水平探讨miR-223通过调控HNMT的表达而参与特应性皮炎病理过程的具体作用机制。特应性皮炎是一种病因复杂的炎症性皮肤病。MiR-223在粒细胞、单核细胞、肥大细胞等骨髓来源细胞的系统发育中起着重要作用。在本课题组的前期研究中，发现miR-223在特应性皮炎患者的血清、血细胞及皮肤组织中均显著升高，并且验证了组胺N-甲基转移酶（HNMT）是miR-223的靶点之一。但是，miR-223在特应性皮炎中的作用仍需进一步验证，其参与特应性皮炎病理过程的具体机制也尚未明确。因此，本项目为临床治疗特应性皮炎提供新的理论依据，并阐明了“miR-223—HNMT—组胺代谢—特应性皮炎”这一致病途径。