目的:探讨调控PDGF/PDGFR通路对心肌缺血再灌注损伤(MI/RI)后心室重构的作用及相关机制。方法:建立小鼠MI/RI模型,在PDGFR磷酸化抑制剂CP-673,451干预后,采用心脏超声心超检测心功能,Masson染色检测心肌纤维化,qPCR法测定炎症因子的表达...目的:探讨调控PDGF/PDGFR通路对心肌缺血再灌注损伤(MI/RI)后心室重构的作用及相关机制。方法:建立小鼠MI/RI模型,在PDGFR磷酸化抑制剂CP-673,451干预后,采用心脏超声心超检测心功能,Masson染色检测心肌纤维化,qPCR法测定炎症因子的表达;分离新生大鼠心肌成纤维细胞(neonatal rat cardic fibroblasts,NCF),采用qPCR分析其胶原合成基因的表达,Western印迹法分析p38分子磷酸化水平。结果:CP-673,451可改善小鼠MI/RI后LVEF、FS、LVIDs等心功能指标(P<0.05),减轻MI/RI后心肌纤维化程度;CP-673,451可有效抑制MI/RI后梗死处心肌内炎症因子IL-1β,TNF-α,IL-6 mRNA表达水平(P<0.05),降低NCF中PDGF-BB导致的ColⅠ及ColⅢmRNA的升高程度(P<0.05),降低PDGF-BB刺激的p38蛋白磷酸化水平(P<0.05)。结论:在MI/RI过程中,抑制PDGF/PDGFR通路可下调梗死心肌中炎症反应和胶原合成,从而改善心室重构,这可能通过p38/MAPK信号通路发挥作用。展开更多
The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1...The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1)represents a therapeutic target and its regulating mechanism in GC.GIPC1 expression was elevated in GC tissues,liver metastasis tissues,and lymph node metastases.GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor(PDGFR)/PI3K/AKT signaling pathway,and inhibited the proliferation and migration of GC cells.Conversely,GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway,and promoted GC cell proliferation and migration.Furthermore,platelet-derived growth factor subunit BB(PDGF-BB)cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 expression.Moreover,GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice,while GIPC1 overexpression had contrasting effects.Taken together,our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.展开更多
文摘目的:探讨调控PDGF/PDGFR通路对心肌缺血再灌注损伤(MI/RI)后心室重构的作用及相关机制。方法:建立小鼠MI/RI模型,在PDGFR磷酸化抑制剂CP-673,451干预后,采用心脏超声心超检测心功能,Masson染色检测心肌纤维化,qPCR法测定炎症因子的表达;分离新生大鼠心肌成纤维细胞(neonatal rat cardic fibroblasts,NCF),采用qPCR分析其胶原合成基因的表达,Western印迹法分析p38分子磷酸化水平。结果:CP-673,451可改善小鼠MI/RI后LVEF、FS、LVIDs等心功能指标(P<0.05),减轻MI/RI后心肌纤维化程度;CP-673,451可有效抑制MI/RI后梗死处心肌内炎症因子IL-1β,TNF-α,IL-6 mRNA表达水平(P<0.05),降低NCF中PDGF-BB导致的ColⅠ及ColⅢmRNA的升高程度(P<0.05),降低PDGF-BB刺激的p38蛋白磷酸化水平(P<0.05)。结论:在MI/RI过程中,抑制PDGF/PDGFR通路可下调梗死心肌中炎症反应和胶原合成,从而改善心室重构,这可能通过p38/MAPK信号通路发挥作用。
基金supported by the Natural Science Foundation of Xiamen City(3502Z20227307)the National Natural Science Foundation of China(81472458,82372809)the Special Fund for Public Welfare Research Institutes of Fujian Province(2023R1001001,2023R1001003,2023R1035).
文摘The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1)represents a therapeutic target and its regulating mechanism in GC.GIPC1 expression was elevated in GC tissues,liver metastasis tissues,and lymph node metastases.GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor(PDGFR)/PI3K/AKT signaling pathway,and inhibited the proliferation and migration of GC cells.Conversely,GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway,and promoted GC cell proliferation and migration.Furthermore,platelet-derived growth factor subunit BB(PDGF-BB)cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 expression.Moreover,GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice,while GIPC1 overexpression had contrasting effects.Taken together,our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.
