生物
XBP1型
未折叠蛋白反应
细胞生物学
角质形成细胞
细胞分化
内质网
丝状蛋白
干细胞
Wnt信号通路
信号转导
免疫学
细胞培养
基因
遗传学
核糖核酸
RNA剪接
特应性皮炎
作者
Fiona E. Chalmers,Saie Mogre,Bipin Rimal,Jeongin Son,Andrew D. Patterson,Douglas B. Stairs,Adam B. Glick
标识
DOI:10.1016/j.ydbio.2022.09.009
摘要
The IRE1α-XBP1s signaling branch of the unfolded protein response is a well-characterized survival pathway that allows cells to adapt to and resolve endoplasmic reticulum stress. Recent data has broadened our understanding of IRE1α-XBP1s signaling beyond a stress response and revealed a physiological mechanism required for the differentiation and maturation of a wide variety of cell types. Here we provide evidence that the IRE1α-XBP1s signaling pathway is required for the proliferation and maturation of basal keratinocytes in the mouse tongue and esophageal epithelium. Mice with conditional targeted deletion of either Ire1α or Xbp1 in keratin 14 expressing basal keratinocytes displayed severe thinning of the lingual and esophageal mucosa that rendered them unable to eat. In IRE1α null epithelium harvested at an earlier timepoint, genes regulating cell proliferation, cell-cell adhesion, and keratinization were significantly downregulated; indirect immunofluorescence revealed fewer proliferating basal keratinocytes, downregulation of E-cadherin, and thinning of the loricrin-positive granular and cornified layers. The number of Tp63-positive basal keratinocytes was reduced in the absence of IRE1α, and expression of the Wnt pathway transcription factor LEF1, which is required for the proliferation of lingual transit amplifying cells, was also significantly downregulated at the transcript and protein level. Together these results reveal an essential role for IRE1α-XBP1s in the maintenance of the stratified squamous epithelial tissue of the tongue and esophagus.
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