Page 60 - 南京医科大学学报自然科学版

南京医科大学学报（自然科学版） 第43卷第6期
·802 · Journal of Nanjing Medical University（Natural Sciences） 2023年6月

·基础研究·

缺氧下调FTO并促进小鼠肺动脉平滑肌细胞迁移

史薪炜，钱 骏，袁 超，史阳阳，孙 凯 *
南京医科大学第一附属医院急诊医学科，江苏 南京 210029

［摘 要］ 目的：探究脂肪质量与肥胖相关蛋白（fat mass and obesity associated protein，FTO）对缺氧小鼠肺动脉平滑肌细胞
（mouse pulmonary artery smooth muscle cell，MPASMC）迁移能力的影响。方法：体外培养 MPASMC，用三气培养箱构建缺氧
MPASMC 模型；免疫印迹实验用于检测FTO蛋白表达；FTO过表达以及敲低质粒转染MPASMC 以过表达或抑制FTO表达；细
胞划痕实验检测细胞迁移能力。结果：缺氧培养后的MPASMC中FTO蛋白表达明显下调，划痕实验提示细胞迁移加快，并在
过表达FTO后明显减慢；常氧状态下敲低FTO表达出现了类似缺氧培养的“促迁移”表型。结论：在体外条件下MPASMC缺氧
培养后FTO蛋白水平下调，细胞迁移能力增强，并且FTO可能是促进MPASMC迁移的关键调控基因。
［关键词］ 肺高压；脂肪质量与肥胖相关蛋白；细胞迁移
［中图分类号］ R544.16 ［文献标志码］ A ［文章编号］ 1007⁃4368（2023）06⁃802⁃05
doi：10.7655/NYDXBNS20230608

Hypoxia down⁃regulates FTO and promotes migration of mouse pulmonary artery smooth
muscle cells

*
SHI Xinwei，QIAN Jun，YUAN Chao，SHI Yangyang，SUN Kai
Department of Emergency Medicine，the First Affiliated Hospital of Nanjing Medical University，Nanjing 210029，
China

［Abstract］ Objective：The current study aims to investigate the effect of fat mass and obesity associated protein（FTO）on the
migration of hypoxia⁃inoluced pulmonary artery smooth muscle cells（PASMC）. Methods：MPASMC was cultured in vitro. The hypoxia
model of MPASMC was established in a three⁃gas incubator（37℃，1%O2，5%CO2 ）. The expression of FTO protein was detected by
Western blot. FTO overexpression and knockdown plasmids were transfected into MPASMC to over⁃express or inhibit FTO expression，
respectively. Cell wound healing assay was used to detect cell migration ability. Results：The expression of FTO protein in MPASMC after
hypoxia culture was significantly down⁃regulated. Wound healing assay indicated that MPASMC migration was accelerated after hypoxia
culture and was significantly slowed down after FTO overexpression in MPASMC. Knockdown FTO expression in MPASMC in normoxia
showed a“pro⁃migration”phenotype similar to hypoxic culture. Conclusion：Under hypoxic conditions，the expression of FTO protein is
down⁃regulated in MPASMC and the cells migration ability is enhanced. FTO may be a key regulator of MPASMC migration.
［Key words］ pulmonary hypertension；fat mass and obesity associated protein；cell migration
［J Nanjing Med Univ，2023，43（06）：802⁃806］

肺高压（pulmonary hypertension，PH）是一类由 monary vascular remodeling，PVR）是 PH 发展过程中
多种病因和发病机制引起肺血管结构和功能障碍， 的关键环节，包括肺动脉平滑肌细胞（pulmonary
进而导致肺循环阻力和肺动脉压力升高的临床综 artery smooth muscle cell，PASMC）的异常增殖和迁
［2］
合征。缺氧是 PH 最常见的原因之一，能促进肺血 移 ，其中PASMC向内膜的迁移往往预示着肺动脉
［1］ ［3］
管持续收缩，增加肺循环阻力 。肺血管重构（pul⁃ 的不可逆增厚和肌化，PVR过程难以逆转 。脂肪质
［基金项目］ 国家自然科学基金（81871544）；江苏省自然科 量和肥胖相关蛋白（fat mass and obesity associated
［4］
学基金（BK20181493） protein，FTO）与机体能量摄入以及代谢调节相关 ，
∗ 也是最早被发现的 m6A（N6⁃methyladenosine）去甲
通信作者（Corresponding author），E⁃mail：sunkai@njmu.edu.cn