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尼古丁乙胆受体信号保持了表皮屏障的完整性

Nadja S Katheder¹, Kristen C Browder¹, Diana Chang²

¹Regenerative Medicine, Genentech, South San Francisco, United States.

|December 8, 2023

概括

这项研究使用果来识别与慢性阻塞性肺病 (COPD) 和炎症性肠病相关的基因. 研究人员发现,尼古丁乙胆受体 (nAchR) 信号传递对于维持上皮屏障功能和肠道平衡至关重要.

科学领域:

遗传学和分子生物学
皮质生物学皮质生物学
模型生物研究模型生物研究

背景情况:

表皮屏障的破坏是慢性肺和肠道疾病的核心,如COPD和炎症性肠道疾病.
人类遗传学研究已经确定了风险位置,但特定的基因和功能在很大程度上是未知的.
候选基因的功能验证需要强大的模型系统.

研究的目的:

快速识别和优先考虑与COPD风险局部相关的基因,使用模型生物选.
为了功能性地描述已识别的基因在维护上皮质屏障完整性的作用.
研究尼古丁乙胆受体 (nAchR) 信号传导在上皮质平衡中的特定作用.

主要方法:

在 *Drosophila melanogaster* (果) 中进行了大规模的基因查,使用肠道屏障功能障碍作为读取结果.
通过全人类基因组关联研究 (GWAS) 确定的验证的候选COPD风险基因.
在肠细胞中执行了nAchR亚单元基因的功能性特征.

主要成果:

在56%的测试基因中成功验证了候选基因扰动对表皮屏障功能的影响,生成了优先级列表.
确定了尼古丁性乙胆受体 (nAchR) 在肠细胞中发出信号,这对表皮屏障功能至关重要.
证明nAchR信号调节周围质矩阵的产生,从而促进上皮质平衡.

结论:

鉴定出新的COPD相关基因,这些基因对于维持上皮屏障至关重要.
提供了关于表皮的nAchR信号在维持肠道平衡中的作用的功能性见解.
确立了 *Drosophila* 作为优先考虑和研究涉及慢性退行性呼吸道和肠道疾病的基因的强大模型.

关键词:

慢性慢性肺炎是一种慢性慢性肺炎,COPD是一种慢性肺炎.D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. melanogaster. D. melanogaster. melanogaster. D. melanogaster. D. melanogaster. melanogaster. D.在GWAS中,GWAS就是GWAS.乙烯基胆是一种遗传学遗传学遗传学是一个基因组学就是基因组学.免疫学免疫学免疫学这是一种炎症炎症炎症炎症.肠道屏障肠道屏障肠道屏障

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