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负责1b型糖原储存疾病的基因SLC37A4通过JAM1表达调节牙上皮质屏障功能
Keita Tanigaki1, Risako Matsumura2, Naoko Sasaki3
1Department of Preventive Dentistry, Osaka University Dental Hospital, Suita, Osaka, 565-0871, Japan.
Scientific reports
|October 21, 2024
概括
溶性载体家族37成员4 (SLC37A4) 通过调节HMX3和JAM1表达,影响牙屏障功能. 这解释了在糖原储存疾病1b型 (GSD1b) 牙周炎中观察到的减少的屏障功能.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 溶性载体家族37成员4 (SLC37A4) 对于葡萄糖恒温至关重要,其功能障碍会导致1b型 (GSD1b) 型的葡萄糖储存疾病.
- GSD1b患者经常患上牙周炎,但根本的分子机制尚未完全理解.
研究的目的:
- 研究SLC37A4在维持牙上皮细胞屏障功能中的作用.
- 为了阐明将SLC37A4与牙屏障完整性联系起来的分子途径.
主要方法:
- 使用了不朽化的人类牙上皮质 (IHGE) 细胞和3D多层牙上皮质组织模型.
- 进行了SLC37A4淘汰和HMX3淘汰/过度表达实验.
- 评估了JAM1的表达和细胞对LPS和peptidoglycan的透性.
主要成果:
- 在IHGE细胞中SLC37A4的淘汰会减少JAM1的表达,并增加透性.
- 鉴定出H6家族 homeobox 3 (HMX3) 是一个调节JAM1.1的关键转录因子.
- SLC37A4缺乏导致HMX3水平下降,这被HMX3过度表达所挽救,恢复了JAM1的表达.
结论:
- SLC37A4通过HMX3/JAM1通路调节牙上皮质屏障功能.
- 这项研究为GSD1b患者牙周炎敏感性增加提供了分子基础.
- 针对SLC37A4-HMX3-JAM1轴可能为GSD1b相关的牙周炎提供治疗策略.
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