Hippo dictates signaling for cellular homeostasis and immune defense in Crassostrea hongkongensis hemocytes.
Hippo dictates signaling for cellular homeostasis and immune defense in Crassostrea hongkongensis hemocytes.
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DOI：
10.3389/fimmu.2023.1173796
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发表时间：
2023
影响因子：
7.3
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中科院分区：
文献类型：
--
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河马信号通路是一个进化上保守的信号级联，在调节细胞的增殖、分化和凋亡方面起着至关重要的作用。在各种免疫过程中，它被证明是细胞命运和细胞动态平衡的关键调节因子。尽管它在脊椎动物免疫中的功能已经确立，但它在海洋无脊椎动物免疫中的作用仍然知之甚少。因此，我们目前的工作为河马途径如何协调香港牡蛎的血细胞功能提供了新的机制见解，对动物进化中河马途径的主要形式和修饰的研究具有重要意义。从香港华支睾吸虫基因组中鉴定出全套河马途径基因，包括SAV1、MOB1、LATS、YAP/TAZ、TEAD和MST。用定量聚合酶链式反应检测细菌攻击前后不同组织中这些基因的表达水平和血细胞中这些基因的表达水平。这项研究还检测了河马途径与其他免疫途径之间的串扰，例如依赖AP-1和P53的p21信号级联。RNA干扰被用来敲除MST和TEAD，而MST是非规范河马信号的核心协调者，以研究其对血细胞吞噬和细菌清除的影响。结果表明，河马途径的成员在血细胞中高度表达，在细菌攻击后其表达水平显著增加。河马途径和其他免疫途径之间的串扰触发了血细胞凋亡，其功能类似于果蝇和哺乳动物中典型的MST-LATS-YAP信号通路。击倒MST导致吞噬功能增强，并提高血细胞中细菌的清除效率，这可能是由于NRF动员抗氧化剂转录来维持免疫平衡。这项研究为河马途径在香港华支睾吸虫血细胞免疫反应中的调节机制提供了新的见解。这项研究强调了河马途径在维持牡蛎免疫平衡和协调血细胞功能方面的重要性。此外，这项研究表明，河马途径在海洋无脊椎动物免疫中的作用与哺乳动物的观察结果存在差异，表明有必要进行进一步的跨物种比较研究。这些发现对未来旨在阐明河马信号通路在动物进化中的进化轨迹和功能多样性的研究具有重要意义。
The Hippo signaling pathway is an evolutionarily conserved signaling cascade that plays a crucial role in regulating cell proliferation, differentiation, and apoptosis. It has been shown to be a key regulator of cell fate and cellular homeostasis in various immune processes. Despite its well-established functions in vertebrate immunity, its roles in marine invertebrate immunity remain poorly understood. Therefore, our present work provides fresh mechanistic insights into how the Hippo pathway orchestrates hemocytic functions in Crassostrea hongkongensis, with implications for studies on its major forms and modifications in animal evolution. The complete set of Hippo pathway genes, including SAV1, MOB1, LATS, YAP/TAZ, TEAD, and MST, were identified from the C. hongkongensis genome. Quantitative PCR assays were conducted to examine the mRNA expression levels of these genes in different tissues and the levels of these genes in hemocytes before and after bacterial challenges. The study also examined the crosstalk between the Hippo pathway and other immune pathways, such as the AP-1 and p53-dependent p21 signaling cascades. RNA interference was used to knock down MST and TEAD, and MST is a core orchestrator of non-canonical Hippo signaling, to investigate its impact on phagocytosis and bacterial clearance in hemocytes. The results demonstrated that members of the Hippo pathway were highly expressed in hemocytes, with their expression levels significantly increasing following bacterial challenges. Crosstalk between the Hippo pathway and other immune pathways triggered hemocytic apoptosis, which functioned similarly to the canonical Mst-Lats-Yap signaling pathway in Drosophila and mammals. Knocking down MST resulted in increased phagocytosis and boosted the efficiency of bacterial clearance in hemocytes, presumably due to mobilized antioxidant transcription by Nrf for maintaining immune homeostasis. This study provides novel insights into the regulatory mechanisms underlying the Hippo pathway in immune responses of C. hongkongensis hemocytes. The study highlights the importance of the Hippo pathway in maintaining immune homeostasis and orchestrating hemocytic functions in oysters. Moreover, this study demonstrates the divergence of the Hippo pathway's roles in marine invertebrate immunity from mammalian observations, indicating the need for further comparative studies across species. These findings have significant implications for future research aimed at elucidating the evolutionary trajectory and functional diversity of the Hippo signaling pathway in animal evolution.
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影响因子：
64.5
作者：
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影响因子：
64.5
作者：
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Koul, Hari K.
DOI：
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发表时间：
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期刊：
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影响因子：
--
作者：
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通讯作者：
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