登革热病毒感染改变了内皮间的结点,并促进了人体微血管内皮细胞的内皮 - 半神经 - 过渡性变化
Manuela Escudero-Flórez1, David Torres-Hoyos1, Yaneth Miranda-Brand1
1Molecular and Translation Medicine Group, University of Antioquia, Medellin 050010, Colombia.
Viruses
|July 29, 2023
概括
登革热病毒 (DENV) 感染触发了内皮细胞改变其功能和增加运动,由c-ABL激酶活性驱动. 这一过程通过破坏细胞结合,导致严重的登革热症状.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 严重的登革热的特点是血管泄漏和器官衰竭,源于内皮功能障碍.
- 导致登革热病毒 (DENV) 引起的内皮功能障碍的精确分子机制尚不清楚.
- c-ABL激酶是病毒病原和细胞反应的潜在媒介.
研究的目的:
- 研究c-ABL激酶在DENV诱导的内皮功能障碍中的作用.
- 阐明DENV影响内皮细胞行为和完整性的机制.
主要方法:
- 利用人工miRNA来沉默c-ABL和伊马替尼来抑制其催化活性.
- 感染了DENV-2的内皮细胞,并用来自感染细胞的条件介质处理.
- 评估了c-ABL表达,CRKII酸化,介质细胞和内皮细胞标记水平以及内皮细胞运动性的变化.
主要成果:
- DENV感染和条件介质增加了内皮c-ABL表达和CRKII酸化.
- DENV促进了一个介质细胞表型,由增加的维门/N-cadherin和减少的VE-cadherin/ZO-1证明.
- 抑制或静止c-ABL可以逆转这些DENV诱导的变化,并减少内皮细胞的运动性.
结论:
- DENV感染诱导了c-ABL依赖的内皮表型切换,其特征是细胞-细胞结合的损失.
- 这种表型变化增强了内皮细胞的运动性,有助于严重登革热的发病.
- 向c-ABL激酶可能提供针对DENV诱导的血管并发症的治疗策略.
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