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USP22 通过靶向 TRAF6 促进 诱导的角膜炎中的促炎反应。

USP22 promotes pro‑inflammatory responses in ‑induced keratitis by targeting TRAF6.

机构信息

Department of Ophthalmology, Second Affiliated Hospital of Shandong First Medical University and Shandong Academy of Medical Sciences, Tai'an, Shandong 271000, P.R. China.

Department of Ophthalmology, Tai'an City Central Hospital, Tai'an, Shandong 271000, P.R. China.

出版信息

Mol Med Rep. 2022 May;25(5). doi: 10.3892/mmr.2022.12665. Epub 2022 Mar 4.

Abstract

(PA)‑induced keratitis is characterized by inflammatory epithelial edema, stromal infiltration, corneal ulceration and can lead to vision loss. The present study aimed to study the effect of ubiquitin‑specific protease 22 (USP22) on PA‑induced keratitis. Using RT‑qPCR and western blotting, significantly increased expression of USP22 was identified in mouse corneas and cultured RAW264.7 cells following PA stimulation. In addition, the results of experiments, western blot assay and ELISA suggested that the silencing of USP22 attenuated disease progression, downregulated the NF‑κB pathway and suppressed the expression of pro‑inflammatory cytokines following PA stimulation. Notably, it was identified that the expression of tumor necrosis factor receptor‑associated factor 6 (TRAF6) was decreased by silencing of USP22 and USP22 was found to remove lysine 48‑linked poly‑ubiquitination chains from TRAF6 to stabilize TRAF6 expression and these effects were clearly aggravated following PA infection.

摘要

PA 诱导的角膜炎的特征是炎症性上皮水肿、基质浸润、角膜溃疡,并可导致视力丧失。本研究旨在研究泛素特异性蛋白酶 22 (USP22) 对 PA 诱导的角膜炎的影响。通过 RT-qPCR 和 Western blot 分析,发现 PA 刺激后小鼠角膜和培养的 RAW264.7 细胞中 USP22 的表达明显增加。此外,实验结果、Western blot 分析和 ELISA 表明,USP22 的沉默减弱了疾病的进展,下调了 NF-κB 通路,并抑制了 PA 刺激后的促炎细胞因子的表达。值得注意的是,沉默 USP22 可降低肿瘤坏死因子受体相关因子 6 (TRAF6) 的表达,并且发现 USP22 可从 TRAF6 上去除赖氨酸 48 连接的多泛素化链,从而稳定 TRAF6 的表达,而这些效应在 PA 感染后明显加重。

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