YAP/TAZ-TEAD is a novel transcriptional regulator of genes encoding steroidogenic enzymes in rat granulosa cells and KGN cells
YAP/TAZ-TEAD is a novel transcriptional regulator of genes encoding steroidogenic enzymes in rat granulosa cells and KGN cells
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YAP/TAZ-TEAD 是大鼠颗粒细胞和 KGN 细胞中类固醇生成酶编码基因的新型转录调节因子
DOI：
10.1016/j.mce.2022.111808
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发表时间：
2023
影响因子：
4.1
通讯作者：
Yoshida Yoshio
中科院分区：
文献类型：
--
作者：
Mizutani Tetsuya;Orisaka Makoto;Kawabe Shinya;Morichika Ririko;Uesaka Miki;Yoshida Yoshio
卵泡刺激素（FSH）通过其相关基因的转录调控来调节卵巢颗粒细胞中的类固醇生成。我们在此显示了Hippo通路参与这种调节。在KGN颗粒细胞中，抑制雅普/TAZ活性以TEAD依赖的方式诱导CYP 11 A1、HSD 3 B2和CYP 19 A1的表达，而无cAMP刺激。p38 MAP激酶的选择性抑制剂，抑制雅普/TAZ敲低诱导这些基因的表达，表明该信号可能参与。8 Br-cAMP可诱导这些基因的表达，而典型的雅普/TAZ-TEAD靶基因CYR 61和ADATS 1的表达则受到抑制，表明cAMP的细胞信号转导降低了雅普/TAZ-TEAD活性。组成型活性突变体雅普分别取消了FSH和8 Br-cAMP介导的原代大鼠颗粒细胞和KGN细胞中这些基因的诱导。此外，调控类固醇生成相关基因的雅普/TAZ-TEAD是独立的类固醇生成因子1，类固醇生成的主基因调节器。这些结果表明，雅普/TAZ-TEAD是类固醇生成的负调节因子，FSH对雅普/TAZ-TEAD活性的抑制与卵巢类固醇生成有关。
Steroidogenesis in ovarian granulosa cells is regulated by the follicle-stimulating hormone (FSH) via transcriptional regulation of its related genes. We herein showed the involvement of the Hippo pathway in this regulation. In KGN granulosa cell, repression of YAP/TAZ activity induced the expression ofCYP11A1,HSD3B2, andCYP19A1in a TEAD-dependent manner without cAMP stimulation. A selective inhibitor of p38 MAP kinase, suppressed YAP/TAZ knockdown-indued the expression of these genes, suggesting this signal could be involved. The expression of these genes was induced by 8Br-cAMP, whereas that ofCYR61andADATS1, typical YAP/TAZ-TEAD target genes, was suppressed, suggesting that the cellular signaling of cAMP reduced YAP/TAZ-TEAD activity. The constitutively active mutant YAP canceled the FSH- and 8Br-cAMP-mediated induction of these genes in primary rat granulosa and KGN cells, respectively. Moreover, regulation of steroidogenesis-related genes by YAP/TAZ-TEAD was independent of steroidogenic factor 1, a master gene regulator of steroidogenesis. These results suggest that YAP/TAZ-TEAD is a negative regulator of steroidogenesis and that suppression of YAP/TAZ-TEAD activity by FSH is involved in ovarian steroidogenesis.