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拼接的X盒结合蛋白1的构成表达抑制了小鼠的牙形成

Qian Xu¹, Jiahe Li¹, Hua Zhang¹

¹Department of Biomedical Sciences, Texas A&M University School of Dentistry, Dallas, TX, United States.

Frontiers in physiology

|January 26, 2024

概括

在牙纤维细胞中X-box结合蛋白1异型S (XBP1S) 的构成表达会损害牙和水泥的形成. 持续的XBP1S产生会改变牙细胞的形态和功能,对牙发育产生负面影响.

科学领域:

分子生物学分子生物学
发展生物学发展生物学
细胞生物学细胞生物学

背景情况:

细胞内膜网膜 (ER) 的压力激活了需要内醇的酶1 (IRE1),该酶处理X盒结合蛋白1 (XBP1) mRNA.
拼接XBP1 (XBP1S) 是一种转录因子,对ER应激减轻和分泌细胞分化至关重要.
之前的研究确定了Twist2-Cre;Xbp1(fl/fl) 小鼠用于研究Twist2-表达细胞中的构成性XBP1S表达.

研究的目的:

在Twist2表达细胞中研究具有构成性XBP1S表达的小鼠的牙表型 (Twist2-Cre;Xbp1{fl/fl}小鼠).
确定持续XBP1S表达在牙细胞功能和牙形成中的作用.
分析XBP1S对牙髓腔形态和牙/水泥发育的影响.

主要方法:

一个突变Xbp1s小基因的生成以表达XBP1S独立于IRE1α激活.
免疫组织化学测试以确认构成性XBP1S表达在牙细胞和牙纸细胞中.
放射学,微型CT分析和组织学检查以评估牙科表型.
在现场杂交和免疫组织化学评估基因表达 (Dspp,Dmp1).

主要成果:

构成性XBP1S表达在Twist2-Cre;Xbp1(fl/fl) 小鼠的牙髓细胞和牙髓细胞中得到证实.
在突变小鼠中观察到牙髓腔形态变化和牙/水泥形成显著减少.
组织学分析显示了口腔细胞的形态变化,但牙/水泥密度或DSpp和Dmp1基因的表达没有显著变化.

结论:

持续产生XBP1S会对牙细胞的功能产生不利影响.
构成性XBP1S表达导致牙和水泥形成受损.
这些发现突出了调节的XBP1S活动在维持正常牙发育和质细胞平衡中的关键作用.

关键词:

在X盒结合蛋白1 (XBP1) 中.细胞分化的细胞分化.丹丁·丹丁 (Dentin Dentin) 是一个牙医.牙的生长过程耳鼻细胞质细胞.牙的发育牙的发育

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