DOI: 10.1002/ame2.12221
TRDMT1 exhibited protective effects against LPS - induced inflammation in rats through TLR4- NF- κB / MAPK- TNF - α pathway
Zhengguang Li1
Xiaolong Qi2
Xu Zhang1
Lei Yu1
Lijuan Gao1
Weining Kong2
Wei Chen1
Wei Dong2
Lijun Luo1
Dan Lu1
Lianfeng Zhang3
Yuanwu Ma4
1.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,China2.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,China3.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;Neuroscience Center,Chinese Academy of Medical Sciences,Beijing,China4.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
摘要：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.
机标关键词：throughpathwayratsagainsteffectsexhibitedinducedinflammation
论文发表日期：2022-04-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：11( 172-182 )
英文信息