循环RNA RORβ 调节酒精诱导的纤维细胞与肌纤维细胞分化中的TGFβR1
Viranuj Sueblinvong1, Xian Fan1, Harry Kartmouty-Quintana2
1Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Scientific reports
|September 2, 2025
概括
酒精暴露会增加转化生长因子β (TGFβ) 信号和肺纤维化. 这项研究确定了一条涉及circ-RORβ和miR-140-3p的循环RNA (circRNA) 途径,该途径调解酒精.
科学领域:
- 分子生物学
- 细胞生物学
- 肺病学
背景情况:
- 酒精暴露会加剧转化生长因子β (TGFβ) 信号,促进肺纤维扩散.
- 酒精对TGFβ信号的调节涉及肺部的微RNA (miRNA) 表达变化.
- 连接酒精,miRNA表达和TGFβ信号的确切机制尚不清楚.
研究的目的:
- 阐明循环RNAs (circRNAs) 在酒精诱导的TGFβ信号传递中的作用.
- 研究肺纤维细胞中circ- RORβ,miR- 140- 3p和TGFβ受体1型 (TGFβR1) 的相互作用.
- 在酒精相关的肺损伤中确定针对circ-RORβ-miR-140-3p-TGFβR1轴的治疗潜力.
主要方法:
- 用乙醇处理人类肺纤维细胞,并分析TGFβR1和circ- RORβ水平.
- 在分析中发现miR-140-3p是TGFβR1和circ- RORβ的潜在调节者.
- 实验涉及抑制circ-RORβ或过度表达miR-140-3p,以评估对TGFβR1,纤维蛋白和α-光滑肌肉动蛋白表达和应激纤维形成的影响.
主要成果:
- 乙醇增加了肺纤维细胞中的TGFβR1和circ- RORβ表达.
- 乙醇暴露降低了miR-140-3p水平;circ- RORβ抑制逆转了这种抑制.
- 抑制circ- RORβ减弱的乙醇诱导的TGFβR1,纤维菌素和α- 滑肌动蛋白表达和肌纤维细胞分化.
结论:
- 环-RORβ/miR-140-3p/TGFβR1轴在酒精诱导的TGFβ信号传递中起着至关重要的作用.
- 在酒精暴露的背景下,这种途径有助于纤维细胞与肌纤维细胞的分化.
- 针对circ-RORβ或调节miR-140-3p可能为与酒精有关的肺部疾病提供新的治疗策略.
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