Constitutive expression of spliced X-box binding protein 1 inhibits dentin formation in mice.
Constitutive expression of spliced X-box binding protein 1 inhibits dentin formation in mice.
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DOI：
10.3389/fphys.2023.1319954
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发表时间：
2023
影响因子：
4
通讯作者：
Lu, Yongbo
中科院分区：
文献类型：
--
作者：
Xu, Qian;Li, Jiahe;Zhang, Hua;Wang, Suzhen;Qin, Chunlin;Lu, Yongbo
关键词：
在内质网(ER)胁迫下，肌醇需要酶1(IRE1)被激活，随后将未剪接的X-box结合蛋白1(XBP1U)mRNA转化为拼接的mRNA，编码有效的XBP1s转录因子。XBP1s是缓解内质网应激和分泌细胞分化所必需的。我们以前建立了Twist2-Cre；XBP1 CS/+小鼠，它在Twist2表达细胞和Twist2表达细胞来源的细胞中结构性地表达XBP1。在这项研究中，我们分析了Twist2-Cre；XBP1 CS/+小鼠的牙齿表型。我们首先构建了一个与重组XBP1IRE26等位基因(经过Cre介导重组的XBP1CS等位基因)相对应的Xbp1S微型基因，并在体外证实Xbp1S微型基因表达了不需要Δα激活的XBP1s。免疫组织化学结果显示，XBP1s在Twist2-Cre；XBP1CS/+小鼠的成牙本质细胞和其他牙髓细胞中呈结构性表达。X射线平片和微CT分析显示，与年龄匹配的XBP1 CS/+对照组小鼠相比，XBP1s的结构性表达改变了牙髓室顶部和底部牙本质的形成，导致Twist2-CRE；XBP1 CS/+小鼠的牙本质/牙骨质形成显著减少。然而，牙本质/牙骨质密度在两组小鼠之间没有显著差异。组织学上，XBP1s的持续表达导致了Twist2-Cre；XBP1CS/+小鼠成牙本质细胞的形态变化。然而，原位杂交和免疫组织化学分析表明，持续表达XBP1s对Dspp和Dmp1基因的表达没有明显影响。综上所述，这些结果支持XBP1的持续产生对成牙本质细胞功能和牙本质形成产生不利影响。
Upon endoplasmic reticulum (ER) stress, inositol-requiring enzyme 1 (IRE1) is activated, which subsequently converts an unspliced X-box binding protein 1 (XBP1U) mRNA to a spliced mRNA that encodes a potent XBP1S transcription factor. XBP1S is essential for relieving ER stress and secretory cell differentiation. We previously established Twist2-Cre;Xbp1 CS/+ mice that constitutively expressed XBP1S in the Twist2-expressing cells as well as in the cells derived from the Twist2-expressing cells. In this study, we analyzed the dental phenotype of Twist2-Cre;Xbp1 CS/+ mice. We first generated a mutant Xbp1s minigene that corresponds to the recombinant Xbp1 Δ26 allele (the Xbp1 CS allele that has undergone Cre-mediated recombination) and confirmed that the Xbp1s minigene expressed XBP1S that does not require IRE1α activation in vitro. Consistently, immunohistochemistry showed that XBP1S was constitutively expressed in the odontoblasts and other dental pulp cells in Twist2-Cre;Xbp1 CS/+ mice. Plain X-ray radiography and µCT analysis revealed that constitutive expression of XBP1S altered the dental pulp chamber roof- and floor-dentin formation, resulting in a significant reduction in dentin/cementum formation in Twist2-Cre;Xbp1 CS/+ mice, compared to age-matched Xbp1 CS/+ control mice. However, there is no significant difference in the density of dentin/cementum between these two groups of mice. Histologically, persistent expression of XBP1S caused a morphological change in odontoblasts in Twist2-Cre;Xbp1 CS/+ mice. Nevertheless, in situ hybridization and immunohistochemistry analyses showed that continuous expression of XBP1S had no apparent effects on the expression of the Dspp and Dmp1 genes. In conclusion, these results support that sustained production of XBP1S adversely affected odontoblast function and dentin formation.
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影响因子：
3.7
作者：
Zhang H;Xie X;Liu P;Liang T;Lu Y;Qin C
通讯作者：
Qin C
影响因子：
64.5
作者：
Liu J;Ibi D;Taniguchi K;Lee J;Herrema H;Akosman B;Mucka P;Salazar Hernandez MA;Uyar MF;Park SW;Karin M;Ozcan U
通讯作者：
Ozcan U
影响因子：
13.6
作者：
Huang C;Wu S;Ji H;Yan X;Xie Y;Murai S;Zhao H;Miyagishi M;Kasim V
通讯作者：
Kasim V
影响因子：
11.4
作者：
Lee, AH;Chu, GC;Glimcher, LH
通讯作者：
Glimcher, LH
影响因子：
56.9
作者：
LIOU, HC;BOOTHBY, MR;GLIMCHER, LH
通讯作者：
GLIMCHER, LH