| 1 | TRIM47 is a novel endothelial activation factor that aggravates lipopolysaccharide-induced acute lung injury in mice via K63-linked ubiquitination of TRAF2显示文摘Endothelial activation plays an essential role in the pathogenesis of sepsis-induced acute lung injury,however,the detailed regulatory mechanisms remain largely unknown.Here,we reported that TRIM47,an E3 ubiquitin ligase of the tripartite motifcontaining protein family,was highly expressed in vascular endothelial cells.TRIM47-deficient mice were effectively resistant to lipopolysaccharide(LPS)-induced acute lung injury and death by attenuating pulmonary inflammation.TRIM47 was upregulated during TNFα-induced endothelial activation in vitro.Knockdown of TRIM47 in endothelial cells inhibited the transcription of multiple pro-inflammatory cytokines,reduced monocyte adhesion and the expression of adhesion molecules,and suppressed the secretion of IL-1βand IL-6 in endothelial cells.By contrast,overexpression of TRIM47 promoted inflammatory response and monocyte adhesion upon TNFαstimulation.In addition,TRIM47 was able to activate the NF-κB and MAPK signaling pathways during endothelial activation.Furthermore,our experiments revealed that TRIM47 resulted in endothelial activation by promoting the K63-linked ubiquitination of TRAF2,a key component of the TNFαsignaling pathway.Taken together,our studies demonstrated that TRIM47 as a novel activator of endothelial cells,promoted LPS-induced pulmonary inflammation and acute lung injury through potentiating the K63-linked ubiquitination of TRAF2,which in turn activates NF-κB and MAPK signaling pathways to trigger an inflammatory response in endothelial cells. | Yisong Qian Ziwei Wang Hongru Lin Tianhua Lei Zhou Zhou Weilu Huang Xuehan Wu Li Zuo Jie Wu Yu Liu Ling-Fang Wang Xiao-Hui Guan Ke-Yu Deng Mingui Fu Hong-Bo Xin | 2022 | Signal Transduction and Targeted Therapy2022，7，6： | 2 |
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