The Molecular Mechanism Underlying Pro-apoptotic Role of Hemocytes Specific Transcriptional Factor Lhx9 in Crassostrea hongkongensis.

The Molecular Mechanism Underlying Pro-apoptotic Role of Hemocytes Specific Transcriptional Factor Lhx9 in Crassostrea hongkongensis.
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香港巨牡蛎血细胞特异性转录因子Lhx9促凋亡的分子机制

DOI:
10.3389/fphys.2018.00612
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发表时间:
2018
影响因子:
4
通讯作者:
Yu Z
Yu Z
中科院分区:
医学2区
文献类型:
--
作者:
Zhou Y;Mao F;He Z;Li J;Zhang Y;Xiang Z;Xiao S;Ma H;Zhang Y;Yu Z

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血细胞是软体动物通过炎症、吞噬、包囊等免疫防御病原体的主要器官。宿主免疫系统的良好功能依赖于血细胞的任务发挥和频繁的更新,但潜在的更新机制在基因水平上仍然难以捉摸。在此,我们确定了一个转录因子,LIM同源框9,在近江牡蛎(ChLhx 9),可能参与血细胞凋亡或更新。ChLhx 9含有一个同源结构域和两个LIM结构域。结果表明,ChLhx 9在血细胞中表达量较高,且在细菌攻击下表达量显著增加。与对照组相比,ChLhx 9的RNA干扰显著降低了血细胞的凋亡率,这强烈暗示了其在血细胞中的促凋亡作用。此外,通过RNA-seq检测ChLhx 9基因敲减后的基因组反应,发现与细胞凋亡相关的多种途径,包括凋亡途径、hippo信号途径和p53信号途径均显著下调。同时,ChLhx 9上调了7个关键的凋亡基因,其中ChASPP 1(apoptosis stimulating protein of p53)被证实能强烈诱导血细胞凋亡,这表明ChASPP 1是ChLhx 9介导的导致细胞凋亡的下游靶点。因此,组织特异性转录因子ChLhx 9通过激活凋亡基因或途径诱导牡蛎血细胞凋亡,可能有助于牡蛎血细胞的更新和免疫防御。
Hemocytes are the central organ of immune defense against pathogens by means of inflammation, phagocytosis, and encapsulation in mollusks. The well-functioning of the host immune system relies on the hemocytes’ task exertion and frequent renewal, but the underlying renewal mechanism remains elusive at the gene level. Here, we identified one transcription factor, LIM homeobox 9, in Crassostrea hongkongensis (ChLhx9) that could be involved in hemocyte apoptosis or renewal. ChLhx9 contains a homeodomain and two LIM domains. The expression profile of ChLhx9 showed that it was specific and had high expression in hemocytes, and it significantly increased under the bacterial challenge. RNA interference of ChLhx9 dramatically decreased the apoptosis rate of hemocytes when compared with a control group, which strongly implies its pro-apoptotic role in hemocytes. Furthermore, the genomic responses to the knockdown of ChLhx9 were examined through RNA-seq, which showed that multiple pathways associated with cell apoptosis, including the apoptosis pathway, hippo signal pathway and p53 signaling pathway, were significantly down-regulated. Meanwhile, seven of the key apoptotic genes were confirmed to be upregulated by ChLhx9, among which ChASPP1 (apoptosis stimulating protein of p53) was confirmed to induce hemocyte apoptosis strongly, which demonstrates that ChASPP1 was a downstream target mediated by ChLhx9 that caused apoptosis. In conclusion, tissue-specific transcription factor ChLhx9 induces hemocyte apoptosis through activating apoptotic genes or pathways, which could contribute to hemocyte renewal and immune defense in oysters.
DOI: 10.1093/nar/gkm882
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