犬尿氨酸酶通过促炎作用促进银屑病的发病机制,Journal of Cellular Physiology

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犬尿氨酸酶通过促炎作用促进银屑病的发病机制
Journal of Cellular Physiology ( IF 5.6 ) Pub Date : 2021-09-22 , DOI: 10.1002/jcp.30587
Min Wang ₁ , Yuqian Wang ₁ , Mengdi Zhang ₁ , Qiqi Duan ₁ , Caifeng Chen ₂ , Qiong Sun ₃ , Meng Liu ₁ , Yan Zheng ₁ , Yongping Shao ₁

Affiliation

犬尿氨酸酶 (KYNU) 是色氨酸代谢途径中的关键酶，与正常皮肤相比，其在银屑病病变中的表达升高。然而，KYNU 是否有助于银屑病的发病机制仍然未知。我们试图研究 KYNU 在银屑病中的作用及其可能的调节机制。结果显示，与在银屑病患者样本、IMQ 诱导的 BABL/c 小鼠银屑病样皮肤炎症和 M5 刺激的角质形成细胞系中测定的正常皮肤对照相比，KYNU 在来自患者或动物模型的银屑病皮肤样本中上调。免疫组织化学（IHC）。KYNU 敲低对角质形成细胞增殖的影响微乎其微，但显着抑制 HaCaT、HEKα、和 HEKn 细胞通过定量逆转录聚合酶链反应、酶联免疫吸附测定和蛋白质印迹分析。正如 TargetScan 软件预测的那样，KYNU 的 3'-非翻译区包含皮肤特异性 microRNA (miRNA) miR-203a 的保守靶位点。此外，在 BABL/c 小鼠中 IMQ 诱导的银屑病样皮肤炎症发展过程中，miR-203a 表现出与 KYNU 相反的表达动力学。随后导致 KYNU 抑制的 miR-203 过表达可显着减少角质形成细胞中 M5 诱导的银屑病相关炎症因子的产生。最后，KYNU 抑制剂可以减轻 IMQ 小鼠的病理表型。

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Kynureninase contributes to the pathogenesis of psoriasis through pro-inflammatory effect

Kynureninase (KYNU) is a key enzyme in the tryptophan metabolism pathway with elevated expression in psoriatic lesions relative to normal skin. However, whether KYNU contributes to the pathogenesis of psoriasis remains unknown. We sought to investigate the role of KYNU in psoriasis and its possible regulation mechanism. In the results, KYNU is upregulated in psoriatic skin samples from patients or animal models compared with normal skin control which was assayed in psoriatic patient samples, IMQ-induced psoriasis-like skin inflammation in BABL/c mice and M5-stimulated keratinocyte cell lines by immunohistochemistry (IHC). KYNU knockdown had a trivial impact on keratinocyte proliferation, but significantly inhibited the production of inflammatory cytokines in HaCaT, HEKα, and HEKn cells by quantitative reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and western blot analysis. The 3ʹ-untranslated region of KYNU contains a conserved target site of a skin-specific microRNA (miRNA), miR-203a, as predicted by TargetScan software. Furthermore, miR-203a exhibited an inversed expression kinetics to KYNU during the development of IMQ-induced psoriasis-like skin inflammation in BABL/c mice. Overexpression of miR-203 subsequently leading to the inhibition of KYNU, could significantly reduce the production of M5-induced, psoriasis-related inflammatory factors in keratinocytes. Finally, KYNU inhibitors could alleviate the pathological phenotypes in IMQ-mice. Our study supported the contributive role of KYNU in the development of psoriasis and provided preliminary evidence for KYNU as a potential therapeutic target in psoriasis.

更新日期：2021-09-22

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