全基因组屏幕识别了SEL1L作为一个控制原体循环的细胞内静态
Michael J Podolsky1, Benjamin Kheyfets2, Monika Pandey2
1Department of Medicine, Weill Cornell Medical College, New York, NY, USA. mip9227@med.cornell.edu.
Nature communications
|February 20, 2024
概括
细胞外基质 (ECM) 清除受损有助于纤维化. 一个新发现的细胞反循环,涉及SEL1L,感知原合成以调节ECM清除,提供了对纤维化疾病机制的见解.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 病理学 病理学 病理学
背景情况:
- 细胞外矩阵 (ECM) 清除受损是纤维性疾病的关键因素.
- 虽然ECM清除效应已知,但上游监管机制仍然不太了解.
- 原蛋白是主要的ECM成分,通过细胞外蛋白质解和细胞内碎片的吸收而降解.
研究的目的:
- 为了确定细胞介导的原清除的分子调节者.
- 为了阐明细胞外基质 (ECM) 降解的上游调节.
- 了解纤维化疾病进展背后的细胞机制.
主要方法:
- 用全基因组选来识别调节细胞介导的原清除的基因.
- 研究了原蛋白感知和清除中的内细胞网膜居民蛋白SEL1L的作用.
- 在人类纤维化肺病模型中分析了这种途径的功能.
主要成果:
- 发现了一种新的机制,细胞感知内部原生物合成以调节细胞外原清除.
- 确定SEL1L是这种传感途径的关键组件,通过非正规的功能运行.
- 已经证明,这种途径充当了平静的负反循环,以限制原蛋白的积累.
- 在人类纤维性肺病中观察到这种原清除途径的诱导受损,与病态的原积累相关.
结论:
- 一个细胞自主,静态的原体清除途径,通过SEL1L通过内部原体合成传感调节,对于组织稳定至关重要.
- 这种原清除反循环的失调有助于纤维化肺病中的病态原积累.
- 这一途径通过恢复ECM平衡来代表纤维性疾病的潜在治疗标.
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