期刊
ANIMAL MODELS AND EXPERIMENTAL MEDICINE
卷 5, 期 2, 页码 172-182出版社
WILEY
DOI: 10.1002/ame2.12221
关键词
inflammation; knockout rat; TLR4 pathway; TNF-alpha; Trdmt1
资金
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2021-I2M-1-024, 2021-I2M-1-034]
- Beijing Municipal Natural Science Foundation [M21004]
- National Natural Science Foundation of China [31970508]
- 111 Project of the Ministry of Education [B20095]
This study demonstrates that Trdmt1 plays a protective role in inflammation by regulating the TLR4-NF-kappa B/MAPK-TNF-alpha pathway.
Background: 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. Methods: 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. Results: 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-alpha 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 inflammation by regulating the TLR4-NF-kappa B/MAPK-TNF-alpha pathway. This work provides useful information to understand the TRDMT1 function in inflammation.
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