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 methyltransf...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-induced 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-αlevel 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-αpathway.This work provides useful information to understand the TRDMT1 function in inflammation.展开更多
基金CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I 2M-1-024 and 2021-I 2M-1-034)and Beijing Municipal Natural Science Foundation(M21004)+1 种基金National Natural Science Foundation of China(31970508)111 Project of the Ministry of Education(B20095)。
文摘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-induced 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-αlevel 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-αpathway.This work provides useful information to understand the TRDMT1 function in inflammation.
