The CX3CL1/CX3CR1 signaling axis is established as a pivotal regulator in the pathogenesis of atherosclerosis,with well-documented roles in orchestrating inflammatory responses,mediating immune cell recruitment,and in...The CX3CL1/CX3CR1 signaling axis is established as a pivotal regulator in the pathogenesis of atherosclerosis,with well-documented roles in orchestrating inflammatory responses,mediating immune cell recruitment,and influencing vascular remodeling.This review provides a comprehensive synthesis of current knowledge regarding the structural characteristics and functional properties of the CX3CL1/CX3CR1 pathway.This study delves into its specific mechanistic contributions to atherosclerosis,placing particular emphasis on its regulatory influence across diverse cell types,including arterial endothelial cells,smooth muscle cells,and macrophages.Furthermore,the pathway’s integral involvement in both the initiation and progression of atherosclerotic plaques is dissected,highlighting its critical impact on plaque stability and susceptibility to rupture.The review also extends to the pathogenic significance of CX3CL1/CX3CR1 signaling in atherosclerosis-related comorbidities,incorporating the latest advancements in understanding its roles in coronary heart disease,stroke,and other cardiovascular disorders.By critically integrating findings from the extant literature,this review constructs a foundational framework to guide future investigations and underscores the substantial translational potential of targeting this pathway for therapeutic intervention in clinical settings.展开更多
BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression result...BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCF^(FBXW7),p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCF^(FBXW7),p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCF^(FBXW7)(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCF^(FBXW7) and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCF^(FBXW7),thereby influencing the ubiquitination and degradation of cyclin E1.展开更多
基金Study on the Protective Mechanism of Safflower Yellow Pigment on Vascular Endothelial Function in Patients with Phlegm-Stasis Syndrome Coronary Heart Disease and Stable Angina Pectoris(Project No.20222A010012)Single-Cell Immune Panorama Study on Neiguan(PC6)Acupoint Injection for Improving Pyroptosis in Chronic Heart Failure(Project No.2025A03J3499)+1 种基金The study on the effect and mechanism of Guanxinning Tablets on vascular homeostasis and remodeling in populations with early vascular aging(Project No.2024QC-B1007)Guangzhou Key Laboratory of Traditional Chinese Medicine Rehabilitation(Project No.2024A03J0790).
文摘The CX3CL1/CX3CR1 signaling axis is established as a pivotal regulator in the pathogenesis of atherosclerosis,with well-documented roles in orchestrating inflammatory responses,mediating immune cell recruitment,and influencing vascular remodeling.This review provides a comprehensive synthesis of current knowledge regarding the structural characteristics and functional properties of the CX3CL1/CX3CR1 pathway.This study delves into its specific mechanistic contributions to atherosclerosis,placing particular emphasis on its regulatory influence across diverse cell types,including arterial endothelial cells,smooth muscle cells,and macrophages.Furthermore,the pathway’s integral involvement in both the initiation and progression of atherosclerotic plaques is dissected,highlighting its critical impact on plaque stability and susceptibility to rupture.The review also extends to the pathogenic significance of CX3CL1/CX3CR1 signaling in atherosclerosis-related comorbidities,incorporating the latest advancements in understanding its roles in coronary heart disease,stroke,and other cardiovascular disorders.By critically integrating findings from the extant literature,this review constructs a foundational framework to guide future investigations and underscores the substantial translational potential of targeting this pathway for therapeutic intervention in clinical settings.
基金Supported by Innovative Practice Platform for Undergraduate Students,School of Public Health Xiamen University,No.2021001.
文摘BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCF^(FBXW7),p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCF^(FBXW7),p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCF^(FBXW7)(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCF^(FBXW7) and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCF^(FBXW7),thereby influencing the ubiquitination and degradation of cyclin E1.
