The transcriptomic analysis of gene expression profiles associated with fungal keratitis in mice based on RNA-Seq

Fungal keratitis (FK) is a blinding eye disease with a high incidence in the world. At present, there is no effective treatment for this disease. At the same time, we found that animal organisms have inherent immune response mechanisms to fungal infections such as C-type lectin receptors (CLRs), which can identify fungal invaders and trigger signal transduction pathways and cellular responses to eliminate pathogens. However, previous studies mostly focused on single receptor factors, lacking a systematic analysis of the genetic factors underlying the pathogenesis of FK. Herein,we performed a transcriptomic study of FK in mice model using RNA sequencing to obtain the relevant gene expression profiles and screen the differentially expressed gene sets, signaling pathways and regulatory networks of key genetic factors in the pathogenesis of FK in mice. As a result, several marker genes of FK were identified such as Il1b and Wnt5a. Wnt signaling pathway, cGMP-PKG signaling pathway and Hippo signaling pathway were significantly enriched during fungal infection in mice cornea. In conclusion, our study may provide a novel insights into the pathogenesis of FK as well as more target sites for its drug treatment.

真菌性角膜炎（Fungal keratitis, FK）是一种全球高发的致盲性眼病，目前尚无有效的治疗方案。与此同时，本研究发现动物机体针对真菌感染存在固有免疫应答机制，例如C型凝集素受体（C-type lectin receptors, CLRs）可识别真菌入侵者，进而激活信号转导通路与细胞应答以清除病原体。然而，既往研究多聚焦于单一受体因子，缺乏对真菌性角膜炎发病机制背后遗传因素的系统性分析。为此，本研究通过RNA测序（RNA sequencing）对小鼠真菌性角膜炎模型开展转录组学研究，获取相关基因表达谱，并筛选出小鼠真菌性角膜炎发病过程中关键遗传因子的差异表达基因集、信号通路及调控网络。研究结果显示，本研究鉴定出多个真菌性角膜炎标志物基因，例如Il1b与Wnt5a；小鼠角膜真菌感染过程中，Wnt信号通路、cGMP-PKG信号通路以及Hippo信号通路均发生显著富集。综上，本研究可为真菌性角膜炎的发病机制研究提供全新视角，同时为其药物治疗提供更多潜在靶点。