Background Human interleukin(IL)-37 is a constituent of the IL-1 family with potent anti-inflammatory and immunosuppressive attributes.It has been demonstrated extensive beneficial effects on various diseases;however,...Background Human interleukin(IL)-37 is a constituent of the IL-1 family with potent anti-inflammatory and immunosuppressive attributes.It has been demonstrated extensive beneficial effects on various diseases;however,its role in the pathogenesis of diabetic cardiomyopathy(DCM)remains unclear.Methods In vivo,DCM mouse model was established with streptozotocin injection and a high-fat diet in WT and cardiac fibroblasts(CFs)specific hIL-37b overexpression mice(IL-37-Tg).In vitro,primary mouse CFs were isolated from the hearts of adult mice and cultured with high levels of glucose and palmitic acid.Cardiac function of the mice was assessed using echocardiography.Masson staining,immunofluorescence,western blot and RT-PCR assays were employed to evaluate the expression of cardiac fibrosis and SOCS3-JAK2-STAT3 signaling pathway-related proteins.Results In this study,we found that CFs specific IL-37-Tg significantly ameliorated cardiac dysfunction and reduced collagen production by inhibiting the JAK2-STAT3 axis,as evidenced by the decreased levels of p-JAK2 and p-STAT3 in the heart of CFs specific IL-37-Tg DCM mice.The beneficial effects of IL-37 were consistently observed in CFs treated with high glucose(HG)and palmitic acid(PA).Moreover,we also discovered that the presence of IL-37 increased the expression of SOCS3,a crucial regulator of JAK/STAT signaling,in DCM mice and HG and PA-treated CFs.Finally,the anti-fibrotic action of IL-37 in HG and PAtreated CFs was abolished when either SOCS3 was genetically knocked down or JAK2/STAT3 was pharmacologically activated.Conclusions Our findings indicate that IL-37 exerts its antifibrotic effect by promoting SOCS3-mediated JAK2-STAT3 inactivation and may be considered as a potential therapeutic agent for DCM.展开更多
目的:观察电针对神经病理性疼痛大鼠痛行为学及脊髓细胞因子信号转导抑制蛋白3(SOCS3)表达的影响。方法:SD大鼠随机分为正常组、假手术组、模型组、电针组、非电针组,每组10只。采用坐骨神经结扎压迫建立慢性限制性损伤(CCI)神经痛模型...目的:观察电针对神经病理性疼痛大鼠痛行为学及脊髓细胞因子信号转导抑制蛋白3(SOCS3)表达的影响。方法:SD大鼠随机分为正常组、假手术组、模型组、电针组、非电针组,每组10只。采用坐骨神经结扎压迫建立慢性限制性损伤(CCI)神经痛模型,电针组选取双侧"阳陵泉"、"环跳"穴进行电针治疗,观察大鼠痛行为学和脊髓SOCS3、IL-6基因表达的变化,检测脊髓SOCS3神经细胞定位情况。结果:与模型组相比,电针可显著提高CCI大鼠机械痛及热痛阈值(P<0.01);与正常组相比,模型组大鼠脊髓SOCS3、IL-6 m RNA表达显著上调(P<0.01),而电针可显著降低IL-6m RNA表达,并进一步上调脊髓SOCS3表达水平(P<0.01)。在CCI大鼠中,SOCS3主要表达于脊髓星形胶质细胞和小胶质细胞中。结论:电针可能通过下调IL-6基因表达,并上调SOCS3表达,减轻神经痛大鼠痛敏反应。展开更多
目的观察鼻息肉患者磷酸化信号转导与转录激活因子3(phospho-signal transducers and activators of transcription,p-STAT3)、SOCS3(suppressor of cytokine signaling,SOCS3)及Th17相关因子的水平,初步探讨STAT3及SOCS3对鼻息肉患者T...目的观察鼻息肉患者磷酸化信号转导与转录激活因子3(phospho-signal transducers and activators of transcription,p-STAT3)、SOCS3(suppressor of cytokine signaling,SOCS3)及Th17相关因子的水平,初步探讨STAT3及SOCS3对鼻息肉患者Th17细胞功能的作用。方法选取40例鼻息肉患者标本及15例对照组标本,采用免疫组化和蛋白免疫印迹法检测p-STAT3及SOCS3在鼻息肉组织中的分布及表达,运用ELISA法检测IL-6和IL-17A的表达情况,采用RT-PCR检测RORγt的表达水平,并对数据进行统计学分析。结果鼻息肉组的p-STAT3、IL-6、IL-17A以及RORγt表达明显高于对照组(P<0.01),SOCS3在鼻息肉组中的表达则低于对照组(P<0.01)。相关性分析显示p-STAT3、RORγt及IL-17A与SOCS3呈负相关(p-STAT3/SOCS3:r=-0.545,P<0.01;RORγt/SOCS3:r=-0.627,P<0.05;IL-17A/SOCS3:r=-0.631,P<0.01),而p-STAT3与RORγt、IL-6、IL-17A呈正相关(p-STAT3/RORγt:r=0.594,P<0.001;p-STAT3/IL-6:r=0.632,P<0.001;p-STAT3/IL-17A:r=0.647,P<0.01)。结论 STAT3异常活化,以及SOCS3低表达所致抑制作用缺失可能是造成鼻息肉中Th17细胞过度活化的重要原因。展开更多
肿瘤转移与多种细胞信号通路作用有关,其中与JAK2/STAT3/SOCS3通路关系尤为密切,JAK2/STAT3信号通路的激活参与了肿瘤发生、发展、侵袭和转移等多个环节。细胞因子信号转导抑制蛋白3(suppressors of cytokine signaling 3,SOCS3)负性调...肿瘤转移与多种细胞信号通路作用有关,其中与JAK2/STAT3/SOCS3通路关系尤为密切,JAK2/STAT3信号通路的激活参与了肿瘤发生、发展、侵袭和转移等多个环节。细胞因子信号转导抑制蛋白3(suppressors of cytokine signaling 3,SOCS3)负性调控JAK2/STAT3通路,进而抑制肿瘤的增殖和生长;信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)信号通路的激活促成了肿瘤炎性微环境的形成,参与了肿瘤血管生成、上皮间质转化和细胞外基质降解等多个环节,在肿瘤的侵袭和转移过程中发挥重要作用。本文着重对JAK2/STAT3/SOCS3信号通路与肿瘤转移的关系进行综述,针对JAK2/STAT3/SOCS3细胞信号动态网络在肿瘤中作用机制研究和药物设计为肿瘤治疗提供了新方向。展开更多
基金funded by the National Natural Science Foundation of China(No.81800330)Natural Science Foundation of Shanghai(No.22ZR1414700)Shanghai Pujiang Program(No.21P1401400).
文摘Background Human interleukin(IL)-37 is a constituent of the IL-1 family with potent anti-inflammatory and immunosuppressive attributes.It has been demonstrated extensive beneficial effects on various diseases;however,its role in the pathogenesis of diabetic cardiomyopathy(DCM)remains unclear.Methods In vivo,DCM mouse model was established with streptozotocin injection and a high-fat diet in WT and cardiac fibroblasts(CFs)specific hIL-37b overexpression mice(IL-37-Tg).In vitro,primary mouse CFs were isolated from the hearts of adult mice and cultured with high levels of glucose and palmitic acid.Cardiac function of the mice was assessed using echocardiography.Masson staining,immunofluorescence,western blot and RT-PCR assays were employed to evaluate the expression of cardiac fibrosis and SOCS3-JAK2-STAT3 signaling pathway-related proteins.Results In this study,we found that CFs specific IL-37-Tg significantly ameliorated cardiac dysfunction and reduced collagen production by inhibiting the JAK2-STAT3 axis,as evidenced by the decreased levels of p-JAK2 and p-STAT3 in the heart of CFs specific IL-37-Tg DCM mice.The beneficial effects of IL-37 were consistently observed in CFs treated with high glucose(HG)and palmitic acid(PA).Moreover,we also discovered that the presence of IL-37 increased the expression of SOCS3,a crucial regulator of JAK/STAT signaling,in DCM mice and HG and PA-treated CFs.Finally,the anti-fibrotic action of IL-37 in HG and PAtreated CFs was abolished when either SOCS3 was genetically knocked down or JAK2/STAT3 was pharmacologically activated.Conclusions Our findings indicate that IL-37 exerts its antifibrotic effect by promoting SOCS3-mediated JAK2-STAT3 inactivation and may be considered as a potential therapeutic agent for DCM.
文摘目的:观察电针对神经病理性疼痛大鼠痛行为学及脊髓细胞因子信号转导抑制蛋白3(SOCS3)表达的影响。方法:SD大鼠随机分为正常组、假手术组、模型组、电针组、非电针组,每组10只。采用坐骨神经结扎压迫建立慢性限制性损伤(CCI)神经痛模型,电针组选取双侧"阳陵泉"、"环跳"穴进行电针治疗,观察大鼠痛行为学和脊髓SOCS3、IL-6基因表达的变化,检测脊髓SOCS3神经细胞定位情况。结果:与模型组相比,电针可显著提高CCI大鼠机械痛及热痛阈值(P<0.01);与正常组相比,模型组大鼠脊髓SOCS3、IL-6 m RNA表达显著上调(P<0.01),而电针可显著降低IL-6m RNA表达,并进一步上调脊髓SOCS3表达水平(P<0.01)。在CCI大鼠中,SOCS3主要表达于脊髓星形胶质细胞和小胶质细胞中。结论:电针可能通过下调IL-6基因表达,并上调SOCS3表达,减轻神经痛大鼠痛敏反应。
文摘目的观察鼻息肉患者磷酸化信号转导与转录激活因子3(phospho-signal transducers and activators of transcription,p-STAT3)、SOCS3(suppressor of cytokine signaling,SOCS3)及Th17相关因子的水平,初步探讨STAT3及SOCS3对鼻息肉患者Th17细胞功能的作用。方法选取40例鼻息肉患者标本及15例对照组标本,采用免疫组化和蛋白免疫印迹法检测p-STAT3及SOCS3在鼻息肉组织中的分布及表达,运用ELISA法检测IL-6和IL-17A的表达情况,采用RT-PCR检测RORγt的表达水平,并对数据进行统计学分析。结果鼻息肉组的p-STAT3、IL-6、IL-17A以及RORγt表达明显高于对照组(P<0.01),SOCS3在鼻息肉组中的表达则低于对照组(P<0.01)。相关性分析显示p-STAT3、RORγt及IL-17A与SOCS3呈负相关(p-STAT3/SOCS3:r=-0.545,P<0.01;RORγt/SOCS3:r=-0.627,P<0.05;IL-17A/SOCS3:r=-0.631,P<0.01),而p-STAT3与RORγt、IL-6、IL-17A呈正相关(p-STAT3/RORγt:r=0.594,P<0.001;p-STAT3/IL-6:r=0.632,P<0.001;p-STAT3/IL-17A:r=0.647,P<0.01)。结论 STAT3异常活化,以及SOCS3低表达所致抑制作用缺失可能是造成鼻息肉中Th17细胞过度活化的重要原因。
文摘肿瘤转移与多种细胞信号通路作用有关,其中与JAK2/STAT3/SOCS3通路关系尤为密切,JAK2/STAT3信号通路的激活参与了肿瘤发生、发展、侵袭和转移等多个环节。细胞因子信号转导抑制蛋白3(suppressors of cytokine signaling 3,SOCS3)负性调控JAK2/STAT3通路,进而抑制肿瘤的增殖和生长;信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)信号通路的激活促成了肿瘤炎性微环境的形成,参与了肿瘤血管生成、上皮间质转化和细胞外基质降解等多个环节,在肿瘤的侵袭和转移过程中发挥重要作用。本文着重对JAK2/STAT3/SOCS3信号通路与肿瘤转移的关系进行综述,针对JAK2/STAT3/SOCS3细胞信号动态网络在肿瘤中作用机制研究和药物设计为肿瘤治疗提供了新方向。
