miR-214 在慢性鼻-鼻窦炎黏膜中表达上调，并调节未分化人鼻腔上皮细胞培养物中脂多糖介导的反应。
MiR-214 Expression Is Elevated in Chronic Rhinosinusitis Mucosa and Regulates Lipopolysaccharide-Mediated Responses in Undifferentiated Human Nasal Epithelial Cell Culture.
机构信息
Department of Otolaryngology-Head and Neck Surgery, Shaanxi Provincial People's Hospital, Xi'an, People's Republic of China.
Department of Quality Control, Shaanxi Geological and Mineral Hospital, Xi'an, People's Republic of China.
出版信息
Am J Rhinol Allergy. 2023 Jul;37(4):391-401. doi: 10.1177/19458924231152683. Epub 2023 Feb 16.
BACKGROUND
Chronic rhinosinusitis (CRS) is an inflammatory disorder of the upper airways. MicroRNAs (miRs) are reported to regulate several diverse physiological and pathological processes.
OBJECTIVE
This study aimed to evaluate the impact of miR-214 on lipopolysaccharide (LPS)-mediated inflammation, and mucin 5AC (MUC5AC) expression in human nasal epithelial cells.
METHODS
The expression of miR-214 was detected in CRS with polyps (CRSwNP) and CRS without polyps (CRSsNP) tissues. Cells were treated with LPS and a miR-214 inhibitor. The level of miR-214 was detected by quantitative real-time reverse transcriptase-PCR (qRT-PCR). The inflammatory cytokines (IL-6, IL-8, TNF, and IL-1β) and MUC5AC production were determined by qRT-PCR and ELISA. MUC5AC protein level was detected using western blot. Similarly, we determined the relationship between miR-214 and Sirtuin 1 (SIRT1) using the Dual luciferase activity assay.
RESULTS
miR-214 was increased in CRSwNP and CRSsNP tissues. LPS triggered the expression of miR-214, while miR-214 inhibition diminished the level of miR-214. MiR-214 inhibition prevented LPS-mediated the production of inflammatory cytokines. LPS treatment augmented MUC5AC mRNA, protein levels, and secretion, whereas miR-214 loss inhibited MUC5AC production in the presence of LPS. SIRT1 is a direct target of miR-214. Impairing SIRT1 by siRNA (siSIRT1) or EX527 (a selective SIRT1 inhibitor) reversed the effects of miR-214 inhibitor on inflammation and MUC5AC expression. Furthermore, miR-214 depression inhibited the STAT3/GDF15 pathway via targeting SIRT1. Upregulation of STAT3 or GDF15 partly abolished the anti-inflammatory roles of miR-214 inhibitor.
CONCLUSION
Taken together, miR-214 regulates LPS-mediated inflammation and MUC5AC expression via targeting SIRT1, and STAT3/GDF15 may involve in the regulation of miR-214 inhibitor on inflammation and MUC5AC expression.
背景
慢性鼻-鼻窦炎（CRS）是一种上呼吸道的炎症性疾病。据报道，microRNAs（miRs）可调节多种不同的生理和病理过程。
目的
本研究旨在评估 miR-214 对人鼻上皮细胞中脂多糖（LPS）介导的炎症和粘蛋白 5AC（MUC5AC）表达的影响。
方法
检测息肉性慢性鼻-鼻窦炎（CRSwNP）和非息肉性慢性鼻-鼻窦炎（CRSsNP）组织中 miR-214 的表达。用 LPS 和 miR-214 抑制剂处理细胞。用实时定量逆转录 PCR（qRT-PCR）检测 miR-214 的水平。用 qRT-PCR 和 ELISA 检测炎症细胞因子（IL-6、IL-8、TNF 和 IL-1β）和 MUC5AC 的产生。用 Western blot 检测 MUC5AC 蛋白水平。同样，我们使用双荧光素酶活性测定来确定 miR-214 与 Sirtuin 1（SIRT1）之间的关系。
结果
miR-214 在 CRSwNP 和 CRSsNP 组织中升高。LPS 触发 miR-214 的表达，而 miR-214 抑制降低 miR-214 的水平。miR-214 抑制可防止 LPS 介导的炎症细胞因子的产生。LPS 处理增加 MUC5AC mRNA、蛋白水平和分泌，而 miR-214 缺失抑制 LPS 存在时 MUC5AC 的产生。SIRT1 是 miR-214 的直接靶标。用 siRNA（siSIRT1）或 EX527（一种选择性 SIRT1 抑制剂）抑制 SIRT1 可逆转 miR-214 抑制剂对炎症和 MUC5AC 表达的影响。此外，miR-214 抑制通过靶向 SIRT1 抑制 STAT3/GDF15 通路。STAT3 或 GDF15 的上调部分消除了 miR-214 抑制剂的抗炎作用。
结论
综上所述，miR-214 通过靶向 SIRT1 调节 LPS 介导的炎症和 MUC5AC 表达，STAT3/GDF15 可能参与 miR-214 抑制剂对炎症和 MUC5AC 表达的调节。
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