Lgr4 Regulates Oviductal Epithelial Secretion Through the WNT Signaling Pathway.
Lgr4 Regulates Oviductal Epithelial Secretion Through the WNT Signaling Pathway.
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Lgr4 通过 WNT 信号通路调节输卵管上皮分泌。
DOI：
10.3389/fcell.2021.666303
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发表时间：
2021
影响因子：
5.5
通讯作者：
Pan H
中科院分区：
文献类型：
--
作者：
Tan X;Zhang L;Li T;Zhan J;Qiao K;Wu H;Sun S;Huang M;Zhang F;Zhang M;Li C;Li R;Pan H
WNT信号通路在输卵管/输卵管发育中起着至关重要的作用。然而，在输卵管/输卵管功能中由WNT通路调节的特定生理过程仍然不清楚。受益于LGR 4基因敲除小鼠模型，我们报告了LGR 4对输卵管上皮分泌的调节。具体而言，Lgr 4的缺失改变了小鼠输卵管的大小和重量，严重减少了输卵管上皮细胞的数量，并最终损害了上皮分泌。这些变化是由输卵管上皮细胞质中CTNNB 1蛋白积累的失败，WNT途径的调节，以及随后上皮细胞基因表达谱的深刻变化介导的。此外，在输卵管原代细胞培养系统中，WNT通路的选择性激活通过激活转录因子NR 5A 2触发类固醇生成基因（如Cyp 11 a1和3β-Hsd 1）的表达。如所证明的，LGR 4蛋白调节WNT-NR 5A 2信号级联，促进上皮分泌细胞成熟和类固醇生成，以保护小鼠输卵管发育和功能。
The WNT signaling pathway plays a crucial role in oviduct/fallopian development. However, the specific physiological processes regulated by the WNT pathway in the fallopian/oviduct function remain obscure. Benefiting from the Lgr4 knockout mouse model, we report the regulation of oviduct epithelial secretion by LGR4. Specifically, the loss of Lgr4 altered the mouse oviduct size and weight, severely reduced the number of oviductal epithelial cells, and ultimately impaired the epithelial secretion. These alterations were mediated by a failure of CTNNB1 protein accumulation in the oviductal epithelial cytoplasm, by the modulation of WNT pathways, and subsequently by a profound change of the gene expression profile of epithelial cells. In addition, selective activation of the WNT pathway triggered the expression of steroidogenic genes, like Cyp11a1 and 3β-Hsd1, through the activation of the transcriptional factor NR5A2 in an oviduct primary cell culture system. As demonstrated, the LGR4 protein modulates a WNT-NR5A2 signaling cascade facilitating epithelial secretory cell maturation and steroidogenesis to safeguard oviduct development and function in mice.
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