Background : Inflammation is a complex physiological and pathological process. Although many types of inflammation are well characterized, their physiological func-tions are largely unknown. tRNA aspartic acid methyltransferase 1 (TRDMT1) has been implicated as a stress- related protein, but its intrinsic biological role is unclear. Methods : We constructed a Trdmt1 knockout rat and adopted the LPS-i nduced sepsis model. Survival curve, histopathological examination, expression of inflammatory fac-tors, and protein level of TLR4 pathway were analyzed. Results : Trdmt1 deletion had no obvious impact on development and growth. Trdmt1 de-letion 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 treat-ment 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. Conclusions : Our data demonstrated that Trdmt1 plays a protective role in inflamma-tion by regulating the TLR4- NF- κB/MAPK- TNF-α pathway. This work provides useful information to understand the TRDMT1 function in inflammation.

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;Neuroscience Center,Chinese Academy of Medical Sciences,Beijing,China

[1]Zhengguang Li;Xiaolong Qi;Xu Zhang;Lei Yu;Lijuan Gao;Weining Kong;Wei Chen;Wei Dong;Lijun Luo;Dan Lu;Lianfeng Zhang;Yuanwu Ma-.TRDMT1 exhibited protective effects against LPS - induced inflammation in rats through TLR4- NF- κB / MAPK- TNF - α pathway)[J].动物模型与实验医学（英文）,2022(02):172-182

TRDMT1,Trdmt1,nduced,letion

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