Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medicine College, Beijing, China.
National Human Diseases Animal Model Resource Center and Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Science, Peking Union Medicine College, Chinese Academy of Medical Sciences, Beijing, China.
Animal Model Exp Med. 2022 Apr;5(2):172-182. doi: 10.1002/ame2.12221.
Inflammation is a complex physiological and pathological process. Although many types of inflammation are well characterized, their physiological functions are largely unknown. tRNA aspartic acid methyltransferase 1 (TRDMT1) has been implicated as a stress-related protein, but its intrinsic biological role is unclear.
We constructed a Trdmt1 knockout rat and adopted the LPS-induced sepsis model. Survival curve, histopathological examination, expression of inflammatory factors, and protein level of TLR4 pathway were analyzed.
Trdmt1 deletion had no obvious impact on development and growth. Trdmt1 deletion slightly increased the mortality during aging. Our data showed that Trdmt1 strongly responded in LPS-treated rats, and Trdmt1 knockout rats were vulnerable to LPS treatment with declined survival rate. We also observed more aggravated tissue damage and more cumulative functional cell degeneration in LPS-treated knockout rats compared with control rats. Further studies showed upregulated TNF-α level in liver, spleen, lung, and serum tissues, which may be explained by enhanced p65 and p38 phosphorylation.
Our data demonstrated that Trdmt1 plays a protective role in inflammation by regulating the TLR4-NF-κB/MAPK-TNF-α pathway. This work provides useful information to understand the TRDMT1 function in inflammation.
炎症是一个复杂的生理和病理过程。尽管许多类型的炎症已经得到很好的描述，但它们的生理功能在很大程度上是未知的。天冬氨酸-tRNA 甲基转移酶 1（TRDMT1）已被认为是一种与应激相关的蛋白质，但它的内在生物学作用尚不清楚。
我们构建了 Trdmt1 敲除大鼠，并采用 LPS 诱导的脓毒症模型。分析了生存曲线、组织病理学检查、炎症因子表达和 TLR4 通路的蛋白水平。
Trdmt1 缺失对发育和生长没有明显影响。Trdmt1 缺失在衰老时略微增加了死亡率。我们的数据显示，LPS 处理大鼠中 Trdmt1 强烈响应，Trdmt1 敲除大鼠对 LPS 处理更敏感，生存率下降。与对照组大鼠相比，我们还观察到 LPS 处理的敲除大鼠组织损伤更严重，累积功能细胞变性更多。进一步的研究表明，肝脏、脾脏、肺和血清组织中的 TNF-α 水平升高，这可能是由于 p65 和 p38 磷酸化增强所致。
我们的数据表明，Trdmt1 通过调节 TLR4-NF-κB/MAPK-TNF-α 通路在炎症中发挥保护作用。这项工作为了解 TRDMT1 在炎症中的功能提供了有用的信息。
