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miRNA-34b/c 通过靶向 FGFR1 调节 RSV 感染的气道上皮细胞中的黏液分泌。

miRNA-34b/c regulates mucus secretion in RSV-infected airway epithelial cells by targeting FGFR1.

机构信息

Department of Pediatrics, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.

Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW, Australia.

出版信息

J Cell Mol Med. 2021 Nov;25(22):10565-10574. doi: 10.1111/jcmm.16988. Epub 2021 Oct 12.

Abstract

Respiratory syncytial virus (RSV) infection in airway epithelial cells is the main cause of bronchiolitis in children. Excessive mucus secretion is one of the primary symbols in RSV related lower respiratory tract infections (RSV-related LRTI). However, the pathological processes of mucus hypersecretion in RSV-infected airway epithelial cells remains unclear. The current study explores the involvement of miR-34b/miR-34c in mucus hypersecretion in RSV-infected airway epithelial cells by targeting FGFR1. First, miR-34b/miR-34c and FGFR1 mRNA were quantified by qPCR in throat swab samples and cell lines, respectively. Then, the luciferase reporters' assay was designed to verify the direct binding between FGFR1 and miR-34b/miR-34c. Finally, the involvement of AP-1 signalling was assessed by western blot. This study identified that miR-34b/miR-34c was involved in c-Jun-regulated MUC5AC production by targeting FGFR1 in RSV-infected airway epithelial cells. These results provide some useful insights into the molecular mechanisms of mucus hypersecretion which may also bring new potential strategies to improve mucus hypersecretion in RSV disease.

摘要

呼吸道合胞病毒(RSV)感染气道上皮细胞是导致儿童细支气管炎的主要原因。过度分泌粘液是 RSV 相关下呼吸道感染(RSV 相关 LRTI)的主要标志之一。然而,RSV 感染的气道上皮细胞中粘液过度分泌的病理过程尚不清楚。本研究通过靶向 FGFR1 探讨了 miR-34b/miR-34c 参与 RSV 感染的气道上皮细胞中粘液过度分泌的机制。首先,通过 qPCR 分别在咽喉拭子样本和细胞系中定量检测 miR-34b/miR-34c 和 FGFR1 mRNA。然后,设计荧光素酶报告基因实验来验证 FGFR1 与 miR-34b/miR-34c 的直接结合。最后,通过 Western blot 评估 AP-1 信号通路的参与情况。本研究发现,miR-34b/miR-34c 通过靶向 FGFR1 参与 RSV 感染的气道上皮细胞中 c-Jun 调节的 MUC5AC 产生。这些结果为粘液过度分泌的分子机制提供了一些有用的见解,也可能为改善 RSV 疾病中的粘液过度分泌带来新的潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4249/8581336/689cf4dac350/JCMM-25-10565-g001.jpg

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