Inhibition of NF-κB promotes autophagy via JNK signaling pathway in porcine granulosa cells
Inhibition of NF-κB promotes autophagy via JNK signaling pathway in porcine granulosa cells
复制标题
抑制 NF-κB 通过 JNK 信号通路促进猪颗粒细胞自噬
DOI：
10.1016/j.bbrc.2016.03.101
复制
发表时间：
2016-04-22
影响因子：
3.1
通讯作者：
Zeng, Shen-ming
中科院分区：
文献类型：
--
作者：
Gao, Hui;Lin, Lu;Zeng, Shen-ming
转录因子核因子- κ B （nf - κ B）在细胞增殖和分化、细胞凋亡和炎症等多种过程中发挥重要作用。然而，nf - κ B在猪卵泡发育中的作用尚不清楚。在本研究中，我们发现促卵泡激素（FSH）增加了NF-kappa B （I kappa B）蛋白抑制剂的水平，促进了p65的细胞质定位，表明FSH抑制了猪颗粒细胞NF-kappa B的活化。此外，FSH或另一种NF-kappa B特异性抑制剂吡咯烷二硫代氨基甲酸酯（PDTC）抑制NF-kappa B可以激活JNK信号并增强猪颗粒细胞的自噬活性。通过RNA干扰敲低NF-kappa B的RelA （p65）亚基，消除了JNK信号通路的激活和FSH自噬蛋白表达的增加。同时进一步探讨FSH或pdtc介导的自噬的功能意义。我们的研究结果表明，自噬的增加促进了猪颗粒细胞的孕酮分泌。氯喹阻断自噬可消除FSH或pdtc诱导的黄体酮产生。综上所述，这些结果表明抑制NF-kappa B通过JNK信号通路增加了猪颗粒细胞的自噬，并促进了类固醇的生成。我们的研究结果为自噬在哺乳动物卵泡发育中的调控和功能提供了新的见解。(C) 2016 Elsevier Inc.版权所有。
The transcription factor nuclear factor-kappa B (NF-kappa B) plays an important role in diverse processes, including cell proliferation and differentiation, apoptosis and inflammation. However, the role of NF-kappa B in porcine follicle development is not clearly elucidated. In this study, we demonstrated that follicle stimulating hormone (FSH) increased the level of inhibitor of NF-kappa B (I kappa B) protein and promoted the cytoplasmic localization of p65, indicating that FSH inhibits the activation of NF-kappa B in porcine granulosa cells. Moreover, inhibition of NF-kappa B by FSH or another specific inhibitor of NF-kappa B, pyrrolidine dithiocarbamate (PDTC), could activate JNK signaling and enhance autophagic activity in porcine granulosa cells. Knockdown of RelA (p65) Subunit of NF-kappa B by RNA interference abrogated the activation of JNK signaling pathway and the increase of autophagic protein expression by FSH. Meanwhile, the functional significance of FSH or PDTC-mediated autophagy were further investigated. Our results demonstrated that the increased autophagy promoted progesterone secretion in porcine granulosa cells. Blockage of autophagy by chloroquine obviated the FSH or PDTC-induced progesterone production. Taken together, these results indicate that inhibition of NF-kappa B increased autophagy via JNK signaling, and promote steroidogenesis in porcine granulosa cells. Our results provide new insights into the regulation and function of autophagy in mammalian follicle development. (C) 2016 Elsevier Inc. All rights reserved.