Instituto de Investigaciones Marinas (IIM-CSIC), C/Eduardo Cabello, 6, 36208, Vigo, Spain.
Dev Comp Immunol. 2020 Aug;109:103698. doi: 10.1016/j.dci.2020.103698. Epub 2020 Apr 11.
GDF15 is frequently detected in patients suffering from various diseases, especially those associated with pro-inflammatory processes and/or metabolic disorders. Accordingly, sepsis, whose major complications are related to metabolic alterations and systemic inflammation, significantly increases the secretion of GDF15. Indeed, this cytokine could be considered a marker of sepsis severity. However, until the last several years, the involvement of GDF15 in these disorders had not been widely characterized. In mice, GDF15 was recently described as a pivotal inducer of sepsis tolerance by mediating metabolic alterations that reduce tissue damage. In this work we describe a zebrafish gdf15 gene. We found that gdf15 follows an expression pattern similar to that observed in mammals, being highly expressed in the liver and kidney and induced after pro-inflammatory stimuli. Moreover, larvae overexpressing gdf15 were more resistant to bacterial and viral challenges without affecting the pathogen load. Consequently, Gdf15 also protected zebrafish larvae against LPS-induced mortality. As in mice, zebrafish Gdf15 seems to induce sepsis tolerance by altering the metabolic parameters of the individuals.
生长分化因子 15（GDF15）在患有各种疾病的患者中经常被检测到，尤其是那些与炎症反应过程和/或代谢紊乱相关的疾病。因此，脓毒症的主要并发症与代谢改变和全身炎症有关，会显著增加 GDF15 的分泌。事实上，这种细胞因子可以被认为是脓毒症严重程度的标志物。然而，直到最近几年，GDF15 在这些疾病中的作用还没有得到广泛的描述。在小鼠中，GDF15 最近被描述为通过介导代谢改变来诱导脓毒症耐受的关键诱导因子，从而减少组织损伤。在这项工作中，我们描述了一种斑马鱼 gdf15 基因。我们发现，gdf15 的表达模式与在哺乳动物中观察到的相似，在肝脏和肾脏中高度表达，并在受到促炎刺激后被诱导。此外，过表达 gdf15 的幼虫对细菌和病毒的挑战更具抵抗力，而不会影响病原体载量。因此，Gdf15 还能保护斑马鱼幼虫免受 LPS 诱导的死亡。与在小鼠中一样，斑马鱼 Gdf15 似乎通过改变个体的代谢参数来诱导脓毒症耐受。
