烯酸氧化酶调节表皮分化和屏障完整性在异性食道炎
Masaru Sasaki1, Takeo Hara1, Joshua X Wang1
1Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
氨酸氧化酶 (LOX) 通过激活骨形态蛋白质 (BMP) 途径,有助于维持食道上皮的恒常性和在性食道炎 (EoE) 中的屏障功能. 这个LOX/BMP轴对于食道上皮分化和潜在的治疗点至关重要.
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 生性食道炎 (EoE) 的特征是上皮屏障功能障碍和分化功能受损.
- Lysyl氧化酶 (LOX),一个原交联酶,在 EoE 中在食道上皮上升调,但其功能尚不清楚.
研究的目的:
- 为了研究LOX在人类食道上皮的功能作用.
- 为了确定LOX是否影响表皮分化和屏障完整性,在EoE类炎症的背景下.
主要方法:
- 使用3D有机体和空气-液体接口培养物,用白素-13 (IL-13) 刺激以建模EoE.
- 采用单细胞RNA测序,qPCR,西斑,组织学和功能障碍分析.
- 分析了LOX过度表达对基因表达和信号通路的影响,包括骨形态遗传蛋白 (BMP) 信号.
主要成果:
- 在分化的食道上皮细胞中,IL-13诱导了LOX.
- 洛克斯过度表达改善了分化标记物和增强了屏障完整性 (跨皮质电阻).
- LOX上调BMP2和下调follistatin,激活BMP通路,恢复了上皮平衡.
结论:
- 在炎症期间,LOX充当信号分子,在食道上皮质平衡中发挥非正规的作用.
- 洛克斯/BMP轴对食道上皮分化至关重要,是EoE有前途的治疗标.
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