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| 1 | TRIM14 promotes endothelial activation via activating NF-κB signaling pathway显示文摘Endothelial activation by proinflammatory cytokines is closely associated to the pathogenesis of atherosclerosis and other vascular diseases;however, the molecular mechanisms controlling endothelial activation are not fully understood. Here we identify TRIM14 as a new positive regulator of endothelial activation via activating NF-κB signal pathway. TRIM14 is highly expressed in human vascular endothelial cells (ECs) and markedly induced by inflammatory stimuli such as TNF-α, IL-1β, and LPS. Overexpression of TRIM14 significantly increased the expression of adhesion molecules such as VCAM-1, ICAM-1, E-selectin, and cytokines such as CCL2, IL-8, CXCL-1, and TNF-α in activated ECs and by which it facilitated monocyte adhesion to ECs. Conversely, knockdown of TRIM14 has opposite effect on endothelial activation. Upon TNF-α stimulation, TRIM14 is recruited to IKK complex via directly binding to NEMO and promotes the phosphorylation of IκBα and p65, which is dependent on its K63-linked ubiquitination. Meanwhile, p65 can directly bind to the promoter regions of human TRIM14 gene and control its mRNA transcription. Finally, TRIM14 protein level is significantly upregulated in mouse and human atheroma compared to normal arteries. Taken together, these results indicate that TRIM14-NF-κB forms a positive feedback loop to enhance EC activation and TRIM14 may be a potential therapeutic target for vascular inflammatory diseases such as atherosclerosis. | Xuan Huang Yong Li Xiuzhen Li Daping Fan Hong-Bo Xin Mingui Fu | 2020 | Journal of Molecular Cell Biology2020，12，3： | 3 |
| 2 | 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 |
| 3 | Central role of myeloid MCPIP1 in protecting against LPSinduced inflammation and lung injury显示文摘Although systemic inflammatory responses attributable to infection may lead to significant lung injury,the precise molecular mechanisms leading to lung damage are poorly understood and therapeutic options remain limited.Here,we show that myeloid monocyte chemotactic protein-inducible protein 1(MCPIP1)plays a central role in protecting against LPS-induced inflammation and lung injury.Myeloid-specific MCPIP1 knockout mice developed spontaneous inflammatory syndromes,but at a late age compared to global MCPIP1 knockout mice.Moreover,mice with a myeloid-specific deletion of MCPIP1 were extremely sensitive to LPS-induced lung injury due to overproduction of proinflammatory cytokines and chemokines.We identified C/EBPβand C/EBPδ,two critical transcriptional factors that drive cytokine production and lung injury,as targets of MCPIP1 RNase.LPS administration caused MCPIP1 protein degradation in the lungs.Pharmacological inhibition of MALT1,a paracaspase that cleaves MCPIP1,by MI-2 selectively increased the MCPIP1 protein levels in macrophages and in the lungs.Meanwhile,administration of MI-2 protected mice from LPS-induced inflammation,lung injury and death.Collectively,these results indicate that myeloid MCPIP1 is central in controlling LPS-induced inflammation and lung injury.Pharmacological inhibition of MALT1 protease activity may be a good strategy to treat inflammatory diseases by enhancing MCPIP1 expression in myeloid cells. | Yong Li Xuan Huang Shengping Huang Hui He Tianhua Lei Fatma Saaoud Xiao-Qiang Yu Ari Melnick Anil Kumar Christopher J Papasian Daping Fan Mingui Fu | 2017 | Signal Transduction and Targeted Therapy2017，2，1： | 2 |
| 4 | PDGF induces osteoprotegerin expression in vascular smooth muscle cells by multiple signal pathways 显示文摘 | Mingui Fu David Mylesa | 2002 | Federation of European Biochemical Societies Letters2002，521，： | 1 |
| 5 | MCP-induced protein 1 suppresses TNFα-induced VCAM-1 expression in human endothelial cells显示文摘 | Yongfen Qi Jian Liang Zhi-Gang She Yan Cai Jing Wang Tianhua Lei William B. Stallcup Mingui Fu | 2010 | FEBS Letters2010，，14： | 1 |
| 6 | Activlation of peroxisome proliferator-activated receptor γ inhibits osteoprotegerin gene expression in human aortic smooth muscle cells显示文摘 | Mingui Fu Jifeng Zhang | 2002 | Biochemical and Biophysical Research Communications2002，294，： | 1 |
| 7 | TRIM65 E3 ligase targets VCAM-1 degradation to limit LPS-induced lung inflammation显示文摘Although the adhesion molecules-mediated leukocyte adherence and infiltration into tissues is an important step of inflammation,the post-translational regulation of these proteins on the endothelial cells is poorly understood.Here,we report that TRIM65,an ubiquitin E3 iigase of tripartite protein family,selectively targets vascular cell adhesion molecule 1(VCAM-1)and promotes its ubiq-uitination and degradation,by which it critically controls the duration and magnitude of sepsis-induced pulmonary inflammation.TRIM65 is constitutively expressed in human vascular endothelial cells.During TNFa-induced endothelial activation,the protein levels ofTRIM65 and VCAM-1 are inversely correlated.Expression of wild-type TRIM65,but not expression of aTRIM65 mutant that lacks E3 ubiquitin ligase function in endothelial cells,promotes VCAM-1 ubiquitination and degradation,whereas small interference RNA-mediated knockdown of TRIM65 attenuates VCAM-1 protein degradation.Further experiments show that TRIM65 directly interacts with VCAM-1 protein and directs its polyubiquitination,by which TRIM65 controls monocyte adherence and infiltration into tissues during inflammation.Importantly,TRIM65-deficient mice are more sensitive to lipopolysaccharide-induced death,due to sustained and severe pulmonary inflammation.Taken together,our studies suggest that TRIM65-mediated degradation of VCAM-1 represents a potential mechanism that controls the duration and magnitude of infiammation. | Yong Li Xuan Huang Fang Guo Tianhua Lei Shitao Li Paula Monaghan-Nichols Zhisheng jiang Hong-Bo Xin Mingui Fu | 2020 | Journal of Molecular Cell Biology2020，12，3： | 1 |
| 8 | Peroxisome proliferator activated receptor γ inhibits transforming growth factor β-induced connective tissue growth factor expression in human aortic smooth muscle cells by interfering with Smad3显示文摘 | Fu Mingui Zhang Jifeng Zhu Xiaojun | 2001 | J Biol Chem2001，276，45： | 1 |
| 9 | Peroxisome Peroproliferator activated receptor γ inhibits transforming growth factor β induced connective tissue growth factor expression in human aortic smooth muscle cells by Interfering with Smad3显示文摘 | Fu Mingui Zhang Jifeng Zhu Xiaojun | 2001 | J Biol Chem2001，276，45： | 1 |
| 10 | Activation of peroxisome proliferator-activated receptor γ inhibits osteoprotegerin gene expression in human aortic smooth muscle cells显示文摘 | Mingui Fu Jifeng Zhang Yimin g Lin Xiaojun Zhu Timothy M Willson Yuqing E Chen | 2002 | Biochemical and Biophysical Research Communications2002，，3： | 1 |
| 11 | Peroxisome proliferator activated receptor γ inhibits transforming growth factor β-induced connective tissue growth factor expession in human aortic smooth muscle cell by interfering with S mad 3 显示文摘 | Mingui Fu Jifeng Zhang Xiaojun Zhu | 2001 | J BiolChem2001，276，45： | 1 |
| 12 | Liver LXR[alpha] expression is crucial for whole body cholesterol homeostasis and reverse cholesterol transport in mice显示文摘 | Zhang Yuan Breevoort Sarah R Angdisen Jerry Fu Mingui Schmidt Daniel R Holmstrom Sam R Kliewer Steven A Mangelsdorf David J Schulman Ira G | 2012 | EN2012，，： | 1 |
| 13 | Post-transcriptional gene regulation by RNA-binding proteins in vascular endothelial dysfunction显示文摘Endothelial cell dysfunction is a term which implies the dysregulation of normal endothelial cell functions,including impairment of the barrier functions,control of vascular tone,disturbance of proliferative and migratory capacity of endothelial cells,as well as control of leukocyte trafficking.Endothelial dysfunction is an early step in vascular inflammatory diseases such as atherosclerosis,diabetic vascular complications,sepsis-induced or severe virus infection-induced organ injuries.The expressions of inflammatory cytokines and vascular adhesion molecules induced by various stimuli,such as modified lipids,smoking,advanced glycation end products and bacteria toxin,significantly contribute to the development of endothelial dysfunction.The transcriptional regulation of inflammatory cytokines and vascular adhesion molecules has been well-studied.However,the regulation of those gene expressions at post-transcriptional level is emerging.RNA-binding proteins have emerged as critical regulators of gene expression acting predominantly at the post-transcriptional level in microRNA-dependent or independent manners.This review summarizes the latest insights into the roles of RNA-binding proteins in controlling vascular endothelial cell functions and their contribution to the pathogenesis of vascular inflammatory diseases. | XIN HongBo DENG KeYu FU MinGui | 2014 | Science China(Life Sciences)2014，57，8： | 0 |
| 14 | Increased expression of osteoprotegerin in vascular smooth muscle cells from spontaneously hypertensive rats显示文摘Background Osteoprotegerin (OPG) is a secreted protein of the tumor necrosis factor receptor family, which regulates bone mass by inhibiting osteoclast differentiation and activation. Although OPG is expressed ubiquitously and abundantly in many tissues and cell types including vascular cells, the role of OPG in other tissues is unknown.Our previous studies demonstrated that OPG was highly expressed in vascular smooth muscle cells (VSMC) and upregulated during vascular lesion formation. Methods and Results We documented, by Northern blot analysis,that the expression of OPG was more prevalent in the aorta and cultured VSMC from spontaneously hypertensive rats (SI-IR) compared to Wistar-Kyoto rats (WKY). In addition, we found that the expression of Angiotensin II (Ang II)type I receptor (AT1R) in SHR VSMC was at significantly increased levels than in WKY VSMC. Furthermore, Ang II potently induced the expression of OPG in VSMC in a time- and dose-dependent manner through the AT1R signaling pathway. Conclusions OPG expression was substantially greater in SHR VSMC, suggesting that OPG may be an important determinant of vascular remodeling in SHR. | Yongshan MOU Tianhua LEI Luning ZHAO Xiaojun ZHU Mingui FU Yuqing E CHEN | 2004 | Journal of Geriatric Cardiology2004，1，1： | 0 |
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