Identification of Pharmacological Autophagy Regulators of Active Ulcerative Colitis

作者：Peishan Qiu, Lan Liu, Jun Fang, Meng Zhang, Haizhou Wang, Yanan Peng, Min Chen, Jing Liu, Fan Wang, Qiu Zhao · 发表于：Frontiers in Pharmacology · 年份：2021 · DOI：10.3389/fphar.2021.769718 · 被引用次数：23 · 研究领域：Autophagy in Disease and Therapy、Cancer-related molecular mechanisms research、MicroRNA in disease regulation

Background: Ulcerative colitis (UC) is a chronic recurrent disease of unknown etiology. Recently, it has been reported that autophagy-related gene polymorphism is closely associated with increased risk of UC, and the therapeutic effect of some UC drugs is mediated by regulating autophagy pathways. This study aims to identify pivotal autophagy-related regulators in UC pathogenesis and provide novel molecular targets for the treatment of active UC. Methods: Gene expression profiles and clinical information of active UC patients were obtained from GEO databases. CIBERSORT was adopted to evaluate the immune cell infiltration. We used weighted gene co-expression network analysis (WGCNA) and differential expression analysis to identify the pivotal modules and genes associated with active UC. Subsequently, we conducted validation in the validation set and explored its relationship with commonly used UC therapeutics. Results: 36 healthy controls and 46 active UC patients have been obtained from the training set of GSE53306, GSE87466, and GSE134025. There were 423 differentially expressed genes (DEGs) found, which dramatically enriched in autophagy-related pathways. And more infiltration of mast cells, activated T cells, dendritic cells, and M1 macrophages were observed in the intestinal mucosa of active UC, while more infiltration of resting immune cells and M2 macrophages in healthy controls. WGCNA indicated that the turquoise and blue modules were the critical modules. CASP1, SERPI...