目的研究芍药苷-6-氧-苯磺酸酯(CP-25)通过抑制GRK2活性对骨关节炎(osteoarthritis,OA)小鼠膝关节软骨的保护作用。方法内侧半月板失稳(destabilization of the medial meniscus,DMM)手术诱导构建小鼠骨关节炎模型,实验分为假手术组、...目的研究芍药苷-6-氧-苯磺酸酯(CP-25)通过抑制GRK2活性对骨关节炎(osteoarthritis,OA)小鼠膝关节软骨的保护作用。方法内侧半月板失稳(destabilization of the medial meniscus,DMM)手术诱导构建小鼠骨关节炎模型,实验分为假手术组、模型组、CP-25给药组和帕罗西汀给药组。术后开始灌胃给药。给药12周处死动物,Micro-CT成像观察膝关节软骨退变、骨重塑异常等情况,番红固绿染色观察小鼠关节组织病理,免疫组化、免疫荧光检测软骨组织相关分子表达水平的影响。Western blot检测CP-25用药后软骨细胞的膜蛋白及总蛋白表达水平。结果模型小鼠关节软骨严重退变。CP-25可显著降低关节软骨骨赘数量及软骨下板厚度,促进软骨基质再生,减少软骨基质降解蛋白表达,对膝关节软骨有明显的保护作用。免疫组化和免疫荧光结果显示,CP-25治疗可显著降低膝关节组织中GRK2、ADAMTS5、MMP13的表达,并且升高膝关节组织中ColⅡ、Aggrecan表达。体外实验结果表明,CP-25给药可以显著降低GRK2的膜蛋白及总蛋白表达水平,升高EP4膜蛋白水平,降低MMP13水平。结论CP-25给药可显著促进OA小鼠关节软骨基质再生,减少软骨基质降解,对OA具有治疗作用,其机制与抑制GRK2介导的软骨基质代谢有关。展开更多
Background G-protein–coupled receptor kinases (GRKs) play important roles in cardiac hypertrophy and heart failure. The role of GRK4 in hypertension has been well demonstrated, but little is known in cardiac ischemic...Background G-protein–coupled receptor kinases (GRKs) play important roles in cardiac hypertrophy and heart failure. The role of GRK4 in hypertension has been well demonstrated, but little is known in cardiac ischemic injury. In the present study, we explore if and how GRK4 regulates cardiomyocyte autophagy and influence the prognosis of myocardial infarction (MI).展开更多
Cancer is a multistep process encompassing the transformation of normal epithelial cells to the stromal invasion and metastasis, with these last considered the final stage of the disease. Tumor invasiveness is based o...Cancer is a multistep process encompassing the transformation of normal epithelial cells to the stromal invasion and metastasis, with these last considered the final stage of the disease. Tumor invasiveness is based on creation of a specific peri-tumoral environment which on turn depends upon epithelial-stromal interactions, degradation of extracellular matrix and reorganization of fibrillar components. Even though several aspects of the stromal and cellular remodeling have been elucidated and described, such as the epithelial-mesenchymal transition (EMT) and extracellular matrix degradation, all the underlying molecular mechanism are far to be elucidated in their complexity. In this review we focused on new actors such as microRNAs, G protein coupled receptor kinases (GRKs) and Calcium/calmodulin-dependent protein kinase (CaMKs) known to be involved in several important physiological processes like development, cell differentiation and cell signaling, and more recently linked to tumor progression and invasion.展开更多
文摘目的研究芍药苷-6-氧-苯磺酸酯(CP-25)通过抑制GRK2活性对骨关节炎(osteoarthritis,OA)小鼠膝关节软骨的保护作用。方法内侧半月板失稳(destabilization of the medial meniscus,DMM)手术诱导构建小鼠骨关节炎模型,实验分为假手术组、模型组、CP-25给药组和帕罗西汀给药组。术后开始灌胃给药。给药12周处死动物,Micro-CT成像观察膝关节软骨退变、骨重塑异常等情况,番红固绿染色观察小鼠关节组织病理,免疫组化、免疫荧光检测软骨组织相关分子表达水平的影响。Western blot检测CP-25用药后软骨细胞的膜蛋白及总蛋白表达水平。结果模型小鼠关节软骨严重退变。CP-25可显著降低关节软骨骨赘数量及软骨下板厚度,促进软骨基质再生,减少软骨基质降解蛋白表达,对膝关节软骨有明显的保护作用。免疫组化和免疫荧光结果显示,CP-25治疗可显著降低膝关节组织中GRK2、ADAMTS5、MMP13的表达,并且升高膝关节组织中ColⅡ、Aggrecan表达。体外实验结果表明,CP-25给药可以显著降低GRK2的膜蛋白及总蛋白表达水平,升高EP4膜蛋白水平,降低MMP13水平。结论CP-25给药可显著促进OA小鼠关节软骨基质再生,减少软骨基质降解,对OA具有治疗作用,其机制与抑制GRK2介导的软骨基质代谢有关。
文摘Background G-protein–coupled receptor kinases (GRKs) play important roles in cardiac hypertrophy and heart failure. The role of GRK4 in hypertension has been well demonstrated, but little is known in cardiac ischemic injury. In the present study, we explore if and how GRK4 regulates cardiomyocyte autophagy and influence the prognosis of myocardial infarction (MI).
文摘Cancer is a multistep process encompassing the transformation of normal epithelial cells to the stromal invasion and metastasis, with these last considered the final stage of the disease. Tumor invasiveness is based on creation of a specific peri-tumoral environment which on turn depends upon epithelial-stromal interactions, degradation of extracellular matrix and reorganization of fibrillar components. Even though several aspects of the stromal and cellular remodeling have been elucidated and described, such as the epithelial-mesenchymal transition (EMT) and extracellular matrix degradation, all the underlying molecular mechanism are far to be elucidated in their complexity. In this review we focused on new actors such as microRNAs, G protein coupled receptor kinases (GRKs) and Calcium/calmodulin-dependent protein kinase (CaMKs) known to be involved in several important physiological processes like development, cell differentiation and cell signaling, and more recently linked to tumor progression and invasion.
