Objective:To study the correlation of peripheral blood IL-17A gene polymorphism with myocardial injury and MMPs/TIMPs balance in patients with viral myocarditis.Methods:A total of 80 patients who were diagnosed with v...Objective:To study the correlation of peripheral blood IL-17A gene polymorphism with myocardial injury and MMPs/TIMPs balance in patients with viral myocarditis.Methods:A total of 80 patients who were diagnosed with viral myocarditis in Dongguan Branch, Yan'an University Affiliated Hospital between September 2014 and September 2017 were selected as the VMC group of the research, and 100 healthy volunteers who received physical examination in Dongguan Branch, Yan'an University Affiliated Hospital during the same period were selected as the control group of the research. The peripheral blood was collected to determine the IL-17A gene rs2275913 locus polymorphism, and serum was collected to determine the contents of myocardial injury and MMPs/TIMPs indexes.Results: The proportion of IL-17A gene GG genotype of VMC group was lower than that of control group and the proportion of GA+AA genotype was higher than that of control group;serum IL-17, CK-MB, cTnI, sFas, MDA, PINP, ICTP, MMP2, MMP9, TIMP1 and TIMP2 contents of VMC group were significantly higher than those of control group, and serum IL-17, CK-MB, cTnI, sFas, MDA, PINP, ICTP, MMP2, MMP9, TIMP1 and TIMP2 contents of patients with GA+AA genotype in VMC group were higher than those of patients with GG genotype.Conclusion: The mutation of the allele G to A in the peripheral blood IL-17A gene rs2275913 locus of patients with viral myocarditis can aggravate myocardial injury and MMPs/TIMPs imbalance.展开更多
The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)inductio...The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.展开更多
文摘Objective:To study the correlation of peripheral blood IL-17A gene polymorphism with myocardial injury and MMPs/TIMPs balance in patients with viral myocarditis.Methods:A total of 80 patients who were diagnosed with viral myocarditis in Dongguan Branch, Yan'an University Affiliated Hospital between September 2014 and September 2017 were selected as the VMC group of the research, and 100 healthy volunteers who received physical examination in Dongguan Branch, Yan'an University Affiliated Hospital during the same period were selected as the control group of the research. The peripheral blood was collected to determine the IL-17A gene rs2275913 locus polymorphism, and serum was collected to determine the contents of myocardial injury and MMPs/TIMPs indexes.Results: The proportion of IL-17A gene GG genotype of VMC group was lower than that of control group and the proportion of GA+AA genotype was higher than that of control group;serum IL-17, CK-MB, cTnI, sFas, MDA, PINP, ICTP, MMP2, MMP9, TIMP1 and TIMP2 contents of VMC group were significantly higher than those of control group, and serum IL-17, CK-MB, cTnI, sFas, MDA, PINP, ICTP, MMP2, MMP9, TIMP1 and TIMP2 contents of patients with GA+AA genotype in VMC group were higher than those of patients with GG genotype.Conclusion: The mutation of the allele G to A in the peripheral blood IL-17A gene rs2275913 locus of patients with viral myocarditis can aggravate myocardial injury and MMPs/TIMPs imbalance.
基金National Natural Science Foundation of China(Grants Numbers 81902878 and 81971468).
文摘The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.
