TRDMT1 exhibited protective effects against LPS-induced inflammation in rats through TLR4-NF-κB/MAPK-TNF-α pathway

[摘要] 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-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 inflammation by regulating the TLR4-NF-κB/MAPK-TNF-α pathway. This work provides useful information to understand the TRDMT1 function in inflammation.

[学科分类] 机械工程学

[关键词] inflammation;knockout rat;TLR4 pathway;TNF-α;Trdmt1