前列腺FP和EP2受体激活剂以不同的方式诱导人类结膜纤维细胞的上皮和下皮纤维遗传变化
Yuri Tsugeno1, Tatsuya Sato2,3, Megumi Watanabe1
1Department of Ophthalmology, Sapporo Medical University School of Medicine, Sapporo, Japan.
概括
前列腺体激动剂PGF2α和Omidenepag (OMD) 通过调节纤维细胞增殖和细胞外基质生产来差异影响转化生长因子β (TGF-β2) 诱导的结膜纤维化.
科学领域:
- 眼科医生 眼科 眼科
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 结膜纤维化是痕形成的关键过程,受转化生长因子β (TGF-β2) 的影响.
- 包括FP和EP2在内的前列腺类受体在纤维生成相关的细胞过程中发挥作用.
研究的目的:
- 研究前列腺FP受体激动剂PGF2α和EP2受体激动剂Omidenepag (OMD) 对TGF-β2诱导的结膜纤维化的影响.
- 分析这些激动剂对纤维细胞增殖,代谢活性和细胞外基因表达的影响.
主要方法:
- 利用人类结膜纤维细胞 (HconF) 的二维 (2D) 和三维 (3D) 培养.
- 通过超内皮电阻 (TEER),实时代谢活动和3D球形尺寸/刚度评估平面增殖.
- 细胞外基质 (ECM) 分子和调节器的量化mRNA表达.
主要成果:
- 由TGF-β2诱导的平面增殖减少了PGF2α,增加了OMD.
- 这两种激动剂都改变了线粒体呼吸和糖分处理能力,OMD增强了TGF-β2对最大呼吸的影响.
- 由3D球形度表示的亚皮质增殖,在两种激动剂中都增加,由TGF-β2.2不同调节.
结论:
- 前列腺体FP和EP2受体agonists,PGF2α和OMD,独立地影响纤维细胞增殖和代谢活动.
- 这些激动剂差异调节TGF-β2诱导的结膜纤维化,影响平面和亚皮质增殖途径.
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