Yin You-Cong, Li Xiao-Hui, Rao Xuan, Li Yuan-Jian, Du Jie
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
Department of Pharmacy, The Central Hospital of Shaoyang, Shaoyang, China.
Front Pharmacol. 2022 Sep 28;13:968098. doi: 10.3389/fphar.2022.968098. eCollection 2022.
Stress ulcers are complicated by severe trauma and other critical diseases, the mechanism of which remains unclear. An increasing number of studies have shown that microRNAs (miRNAs) are important regulators of stress responses such as hypoxia, abnormal temperature, and inflammation. The evidence indicates that miRNAs are also involved in regulating stress-induced ulcers. Recently, we demonstrated that gastric mucosal injury induced by aspirin is related to the reduction of glutamate levels by inhibition of cystine/glutamate transporter (xCT) activity. In the present study, the effect of a miRNA/xCT on gastric mucosal injury induced by cold stimulation was investigated. We found that cold stimulation induced gastric mucosa injury with a reduction in glutamate levels and xCT activity and upregulation of miR-143, miR-152, and miR-181 expression. Exogenous glutamate significantly alleviated gastric mucosa injury by cold stimulation. experiments demonstrated that treatment with miR-143, miR-152, or miR-181 mimics directly induced cell damage. The effects of these mimics were alleviated by exogenous glutamate. The present study suggests that miR-143, miR-152, and miR-181 are involved in cold stimulation-induced acute gastric mucosal injury. Furthermore, the regulatory effect of miRNAs on gastric mucosa injury induced by cold stimulation is related to a decrease in glutamate release by reduction of cystine/glutamate transporter activity.
应激性溃疡常并发于严重创伤及其他危重病，但其发病机制尚不清楚。越来越多的研究表明，微小RNA（miRNA）是缺氧、温度异常及炎症等应激反应的重要调节因子。有证据表明，miRNA也参与应激性溃疡的调控。近期，我们发现阿司匹林诱导的胃黏膜损伤与胱氨酸/谷氨酸转运体（xCT）活性受抑制导致的谷氨酸水平降低有关。在本研究中，我们探究了miRNA/xCT对冷刺激诱导的胃黏膜损伤的影响。我们发现冷刺激可导致胃黏膜损伤，同时伴有谷氨酸水平及xCT活性降低，以及miR-143、miR-152和miR-181表达上调。外源性谷氨酸可显著减轻冷刺激所致的胃黏膜损伤。实验表明，用miR-143、miR-152或miR-181模拟物处理可直接诱导细胞损伤。外源性谷氨酸可减轻这些模拟物的作用。本研究提示，miR-143、miR-152和miR-181参与冷刺激诱导的急性胃黏膜损伤。此外，miRNA对冷刺激诱导的胃黏膜损伤的调控作用与胱氨酸/谷氨酸转运体活性降低导致的谷氨酸释放减少有关。
