Liang Wei, Zhang Yingnan, Zhou Liang, Lu Xiaoqin, Finn Margaret E, Wang Wei, Shao Hui, Dean Douglas C, Zhang Lijun, Liu Yongqing
Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Department of Ophthalmology, Third People's Hospital of Dalian, Dalian Medical University, Dalian 116033, China.
iScience. 2022 Mar 8;25(4):104038. doi: 10.1016/j.isci.2022.104038. eCollection 2022 Apr 15.
The cornea is an avascular tissue for vision clarity. Alkali burn could cause severe traumatic damage on the cornea with inflammation and neovascularization (NV), leading to vision reduction and blindness. Mechanisms underlying corneal inflammation and NV are not as clear. We previously reported that Zeb1 is an important factor in corneal NV, and we sought to clarify whether it is also involved in regulation of corneal inflammation. We analyzed the alkali burn-induced corneal inflammation and wound healing in both Zeb1 and Zeb1 littermates through a multidisciplinary approach. We provide evidence that Zeb1 forms a positive regulatory loop with Tgfb to regulate early corneal inflammation by maintenance of immune cell viability and mobility and later wound healing by activation of both Nf-κb and Tgfb-related Stat3 signaling pathways. We believe that ZEB1 is a potential therapeutic target, and inactivation of ZEB1 could be a strategy to treat severe corneal inflammation condition.
角膜是一种无血管组织，以保持视觉清晰。碱烧伤可对角膜造成严重创伤性损伤，引发炎症和新生血管形成（NV），导致视力下降甚至失明。角膜炎症和新生血管形成的潜在机制尚不完全清楚。我们之前报道过Zeb1是角膜新生血管形成的一个重要因素，我们试图阐明它是否也参与角膜炎症的调节。我们通过多学科方法分析了Zeb1及其同窝仔在碱烧伤诱导的角膜炎症和伤口愈合情况。我们提供的证据表明，Zeb1与Tgfb形成正调控环，通过维持免疫细胞的活力和迁移来调节早期角膜炎症，并通过激活Nf-κb和Tgfb相关的Stat3信号通路来调节后期伤口愈合。我们认为ZEB1是一个潜在的治疗靶点，使ZEB1失活可能是治疗严重角膜炎症的一种策略。
