Ammonia induces autophagy via <scp>circ‐IFNLR1</scp>/<scp>miR</scp>‐2188‐5p/<scp>RNF182</scp> axis in tracheas of chickens
Tianyi Zhang, Ting Chen, Wanying Hu, Jichang Li, Mengyao Guo
Abstract
Abstract Ammonia (NH 3 ), an air pollutant in the living environment, has many toxic effects on various tissues and organs. However, the underlying mechanisms of NH 3 ‐induced tracheal cell autophagy remains poorly understood. In present study, chickens and LMH cells were used as NH 3 exposure models to investigate toxic effects. The change of tracheal tissues ultrastructure showed that NH 3 exposure induced autolysosomes. The differential expression of 12 circularRNAs (circRNAs) was induced by NH 3 exposure using circRNAs transcriptome analysis in broiler tracheas. We further found that circ‐IFNLR1 was down‐regulated, and miR‐2188‐5p was up‐regulated in tracheal tissues under NH 3 exposure. Bioinformatics analysis and dual luciferase reporter system showed that circ‐IFNLR1 bound directly to miR‐2188‐5p and regulated each other, and miR‐2188‐5p regulated RNF182. Overexpression of miR‐2188‐5p caused autophagy and its inhibition partially reversed autophagy in LMH cells which were caused by ammonia stimulation or knockdown of circ‐IFNLR1. The expressions of three autophagy‐related genes (LC3, Beclin 1, and BNIP3) were observably up‐regulated. Our results indicated that NH 3 exposure caused autophagy through circ‐IFNLR1/miR‐2188‐5p/RNF182. These results provided new insights for the study of ammonia on environmental toxicology on ceRNA and circRNAs in vivo and vitro.