Recently, Acta Pharmaceutica Sinica B (IF=14.7), a leading medical journal, published online the latest research results of the team of Hu Qinghua/Zhou Mengze from the School of Pharmacy of our university, “Macrophage P2Y6R activation aggravates Macrophage P2Y6R activation aggravates psoriatic inflammation through IL-27-mediated Th1 responses”. Dr. Li Yin of College of Pharmacy is the first author of this paper, and Prof. Qinghua Hu, Assistant Researcher Mengze Zhou of College of Pharmacy and Associate Prof. Huanqiu Li of Soochow University are the co-corresponding authors, and China Pharmaceutical University is the first corresponding organization.
Psoriasis is a complex inflammatory disease caused by a combination of genetic and environmental factors, and is mainly characterized by erythema and scaling of the skin. In psoriatic lesions, interactions between natural and acquired immune cells lead to an increased inflammatory response, but the mechanism of the interaction between the two is unclear. Purine metabolism plays an important role in the pathogenesis of psoriasis. In the state of inflammation or injury, cells release nucleotides as danger signals, and endogenous nucleotides regulate cellular physiological responses by binding to purinergic receptors, but the mechanism of purinergic receptors in psoriasis is unclear.
The present study reveals the critical role of purine receptor P2Y6R in the development of psoriasis. By studying the expression and localization of P2Y6R in psoriasis patients and psoriasis mouse models, it was found that P2Y6R in macrophages has a positive regulatory effect on the disease. In terms of specific mechanism, macrophages release IL-27 through PLCβ/p-PKC/MAPK signaling pathway under the condition of P2Y6R activation, which leads to the increase of Th1 cell differentiation and thus promotes the development of psoriasis. Meanwhile, the novel P2Y6R inhibitor FS-6 obtained by the group through structural modification on the basis of the previous study could significantly improve the symptoms of psoriasis and provide a new therapeutic means for clinical treatment. In summary, this study reveals the role of the UDP-P2Y6R axis in mediating immune cell-to-cell communication in the pathogenesis of psoriasis, and provides a potential new target for the treatment of psoriasis.
In addition, based on the series of studies on purinergic receptors, the team also published a paper entitled “Comprehensive insights into potential roles of purinergic P2 receptors on diseases” in the Journal of Advanced Research (IF=11.4). The team also published a review entitled “Comprehensive insights into potential roles of purinergic P2 receptors on diseases: Signaling pathways involved and potential therapeutics” in the Journal of Advanced Research (impact factor IF=11.4), which systematically introduces the molecular mechanism of purinergic P2 receptors involved in the development of diseases, and provides an opportunity to develop clinical drug candidates that target purinergic signaling. The review systematically introduces the molecular mechanism of purinergic P2 receptor involved in disease development, and provides prospective strategies for the development of clinical drug candidates targeting purinergic signaling. Yanxiao Guo, a master's student of School of Pharmaceutical Sciences (SPS), grade 21, was the first author, and Prof. Qinghua Hu, Assistant Researcher Mengze Zhou, and Associate Prof. Huanqiu Li, School of Pharmaceutical Sciences, Soochow University, were the co-corresponding authors. China Pharmaceutical University is the first corresponding organization.
This research work was supported by the National Natural Science Foundation of China (No. 82304506, No. 82373887, No. 82373725), China Postdoctoral Science Foundation (2022M723513).
Original link: https://doi.org/10.1016/j.apsb.2024.06.008
https://doi: 10.1016/j.jare.2024.03.027
