Department of Dermatology and Venereology, West China Hospital, Sichuan University, Chengdu, China.
Department of Dermatology, Chengdu Second People's Hospital, Chengdu, China.
Exp Dermatol. 2023 Sep;32(9):1383-1393. doi: 10.1111/exd.14836. Epub 2023 May 23.
Midkine plays a critical role in angiogenesis by regulating the vascular endothelial growth factor (VEGF) signalling pathway, which is known to be associated with psoriasis pathogenesis. However, research on midkine-psoriasis relationship remains limited. The objective of this study was to detect midkine expression in psoriasis and investigate its potential role in the disease. Midkine expression was measured using immunohistochemistry and ELISA. Effects of midkine on HaCaT cell proliferation, VEGF-A production and signalling pathways were assessed using CCK8, RT-PCR and WB. Scratch and in vitro tube formation tests were used to evaluate the effects of HaCaT-cell-activated midkine on the migration and tube formation of human dermal microvascular endothelial cells. Murine psoriasiform models were injected with midkine recombinant protein and midkine monoclonal antibody to investigate skin lesions, tissue sections and dermal microvessel density. Levels of midkine significantly increased in both lesions and serum of patients with psoriasis. Serum expression of midkine decreased after treatment and a positive correlation was found between midkine and disease severity. Midkine promoted HaCaT cell proliferation and VEGF-A production. The Notch2/HES1/JAK2-STAT5A pathway expression increased after midkine treatment of HaCaT cells. The supernatant of HaCaT cells treated with midkine promoted HMEC-1 migration and angiogenesis in vitro. Recombinant midkine protein exacerbated psoriasiform lesions with increased expressions of VEGF-A and microvessel density, while midkine monoclonal antibody alleviated psoriasis lesions. Midkine may have a significant impact on psoriasis angiogenesis by regulating VEGF-A expression through the Notch2/HES1/JAK2-STAT5A pathway, highlighting a potential therapeutic target for psoriasis treatment.
中期因子通过调节血管内皮生长因子（VEGF）信号通路在血管生成中发挥关键作用，已知该通路与银屑病发病机制有关。然而，关于中期因子-银屑病关系的研究仍然有限。本研究旨在检测银屑病中的中期因子表达，并探讨其在疾病中的潜在作用。使用免疫组织化学和 ELISA 检测中期因子表达。使用 CCK8、RT-PCR 和 WB 评估中期因子对 HaCaT 细胞增殖、VEGF-A 产生和信号通路的影响。划痕和体外管形成试验用于评估 HaCaT 细胞激活的中期因子对人真皮微血管内皮细胞迁移和管形成的影响。用中期因子重组蛋白和中期因子单克隆抗体注射鼠类银屑病模型，以研究皮肤病变、组织切片和真皮微血管密度。银屑病患者的病变和血清中中期因子水平显著增加。治疗后血清中期因子表达降低，且中期因子与疾病严重程度呈正相关。中期因子促进 HaCaT 细胞增殖和 VEGF-A 产生。HaCaT 细胞经中期因子处理后 Notch2/HES1/JAK2-STAT5A 通路表达增加。经中期因子处理的 HaCaT 细胞上清液促进 HMEC-1 体外迁移和血管生成。重组中期因子蛋白加剧银屑病样病变，增加 VEGF-A 和微血管密度的表达，而中期因子单克隆抗体缓解银屑病病变。中期因子可能通过 Notch2/HES1/JAK2-STAT5A 通路调节 VEGF-A 表达对银屑病血管生成产生重大影响，为银屑病治疗提供了潜在的治疗靶点。
