The slit diaphragm bridging the neighboring foot processes functions as a final barrier of glomerular capillary wall for preventing the leak of plasma proteins into primary urine.It is now accepted that the dysfunctio...The slit diaphragm bridging the neighboring foot processes functions as a final barrier of glomerular capillary wall for preventing the leak of plasma proteins into primary urine.It is now accepted that the dysfunction of the sit diaphragm contributes to the development of proteinuria in several glomerular diseases.Nephrin,a gene product of NPHS1,a gene for a congenital nephrotic syndrome of Finnish type,constitutes an extracellular domain of the slit diaphragm.Podocin was identified as a gene product of NPHS2,a gene for a familial steroid-resistant nephrotic syndrome of French.Podocin binds the cytoplasmic domain of nephrin.After then,CD2 associated protein,NEPH1 and transient receptor potential-6 were also found as crucial molecules of the slit diaphragm.In order to explore other novel molecules contributing to the development of proteinuria,we performed a subtraction hybridization assay with a normal rat glomerular RNA and a glomerular RNA of rats with a puromycin aminonucleoside nephropathy,a mimic of a human minimal change type nephrotic syndrome.Then we have found that synaptic vesicle protein 2B,ephrin-B1 and neurexin were already downregulated at the early stage of puromycin amino-nucleoside nephropathy,and that these molecules were localized close to nephrin.It is conceivable that these molecules are the slit diaphragm associated molecules,which participate in the regulation of the barrier function.These molecules could be targets to establish a novel therapy for nephrotic syndrome.展开更多
Objective:To explore effect of srGAP3 promotes neurite outgrowth of dorsal root ganglion neurons.Methods:In this study,expression of Slit1 was observed predominantly in the glia.while expression of Robo2 and srCAP3 wa...Objective:To explore effect of srGAP3 promotes neurite outgrowth of dorsal root ganglion neurons.Methods:In this study,expression of Slit1 was observed predominantly in the glia.while expression of Robo2 and srCAP3 was detected in sensory neurons of postnatal rat cultured dorsal root ganglion(DRG).Furthermore,upregulation of srGAP3 following sciatic nerve transection was detected by immunohistochemistry and Western blotting.Results:It was observed that inhibition of nenrite outgrowth in cultured adult DRG neurons following treatment with anti-srGAP3 or anti-Robo2 was more effectively(1.5-fold higher) than that following treatment with an anti-BDNF positive control antibody.It demonstrated that srGAP3 interacted with Robo2 and Slit1 protein to decrease Rac1-CTP activity in cultured adult rat DRG neurons and the opposite effect on Rac1-GTP activity was detected by co-immunoprecipitation and immunoblotting analyses following treatment with anti-Robo2 or anti-srGAP3.These data demonstrated a role for srGAP3 in nenrite outgrowth ol DRG sensory neurons.Conclusions:Our observations suggest that srGAP3 promotes neurile outgrowth and filopodial growth cones by interacting with Robo2 to inactivate Rac1 in mammalian DRG neurons.展开更多
目的研究srGAP2(Slit-Robo GTPase activating Protein 2)、γ-氨基丁酸以及单核细胞趋化蛋白-1(MCP-1)在难治性癫痫患儿脑组织中的表达情况及意义。方法选取11例患儿的颞叶脑组织和同期11例正常标本的颞叶脑组织,使用免疫组化和免疫印...目的研究srGAP2(Slit-Robo GTPase activating Protein 2)、γ-氨基丁酸以及单核细胞趋化蛋白-1(MCP-1)在难治性癫痫患儿脑组织中的表达情况及意义。方法选取11例患儿的颞叶脑组织和同期11例正常标本的颞叶脑组织,使用免疫组化和免疫印迹等方法检测srGAP2、γ-氨基丁酸以及MCP-1的表达情况。结果难治性癫痫患儿脑组织中,srGAP2的阳性表达率显著高于正常脑组织。难治性癫痫患儿脑组织和正常脑组织可以看到染成棕褐色的神经元,但难治性癫痫患儿脑组织γ-氨基丁酸能神经元表达量明显低于正常脑组织。正常脑组织中MCP-1的表达较弱,而难治性癫痫患儿脑组织中MCP-1的表达较强。结论难治性癫痫患儿脑组织srGAP2和MCP-1表达上升而γ-氨基丁酸表达下降,srGAP2、γ-氨基丁酸及MCP-1与难治性癫痫发病密切相关,可能作为潜在治疗靶标。展开更多
文摘The slit diaphragm bridging the neighboring foot processes functions as a final barrier of glomerular capillary wall for preventing the leak of plasma proteins into primary urine.It is now accepted that the dysfunction of the sit diaphragm contributes to the development of proteinuria in several glomerular diseases.Nephrin,a gene product of NPHS1,a gene for a congenital nephrotic syndrome of Finnish type,constitutes an extracellular domain of the slit diaphragm.Podocin was identified as a gene product of NPHS2,a gene for a familial steroid-resistant nephrotic syndrome of French.Podocin binds the cytoplasmic domain of nephrin.After then,CD2 associated protein,NEPH1 and transient receptor potential-6 were also found as crucial molecules of the slit diaphragm.In order to explore other novel molecules contributing to the development of proteinuria,we performed a subtraction hybridization assay with a normal rat glomerular RNA and a glomerular RNA of rats with a puromycin aminonucleoside nephropathy,a mimic of a human minimal change type nephrotic syndrome.Then we have found that synaptic vesicle protein 2B,ephrin-B1 and neurexin were already downregulated at the early stage of puromycin amino-nucleoside nephropathy,and that these molecules were localized close to nephrin.It is conceivable that these molecules are the slit diaphragm associated molecules,which participate in the regulation of the barrier function.These molecules could be targets to establish a novel therapy for nephrotic syndrome.
基金supported by grants from the National Natural Science Foundation of China(81160158)H0911)Hainan Provincial Science and Technology Bureau
文摘Objective:To explore effect of srGAP3 promotes neurite outgrowth of dorsal root ganglion neurons.Methods:In this study,expression of Slit1 was observed predominantly in the glia.while expression of Robo2 and srCAP3 was detected in sensory neurons of postnatal rat cultured dorsal root ganglion(DRG).Furthermore,upregulation of srGAP3 following sciatic nerve transection was detected by immunohistochemistry and Western blotting.Results:It was observed that inhibition of nenrite outgrowth in cultured adult DRG neurons following treatment with anti-srGAP3 or anti-Robo2 was more effectively(1.5-fold higher) than that following treatment with an anti-BDNF positive control antibody.It demonstrated that srGAP3 interacted with Robo2 and Slit1 protein to decrease Rac1-CTP activity in cultured adult rat DRG neurons and the opposite effect on Rac1-GTP activity was detected by co-immunoprecipitation and immunoblotting analyses following treatment with anti-Robo2 or anti-srGAP3.These data demonstrated a role for srGAP3 in nenrite outgrowth ol DRG sensory neurons.Conclusions:Our observations suggest that srGAP3 promotes neurile outgrowth and filopodial growth cones by interacting with Robo2 to inactivate Rac1 in mammalian DRG neurons.
文摘目的研究srGAP2(Slit-Robo GTPase activating Protein 2)、γ-氨基丁酸以及单核细胞趋化蛋白-1(MCP-1)在难治性癫痫患儿脑组织中的表达情况及意义。方法选取11例患儿的颞叶脑组织和同期11例正常标本的颞叶脑组织,使用免疫组化和免疫印迹等方法检测srGAP2、γ-氨基丁酸以及MCP-1的表达情况。结果难治性癫痫患儿脑组织中,srGAP2的阳性表达率显著高于正常脑组织。难治性癫痫患儿脑组织和正常脑组织可以看到染成棕褐色的神经元,但难治性癫痫患儿脑组织γ-氨基丁酸能神经元表达量明显低于正常脑组织。正常脑组织中MCP-1的表达较弱,而难治性癫痫患儿脑组织中MCP-1的表达较强。结论难治性癫痫患儿脑组织srGAP2和MCP-1表达上升而γ-氨基丁酸表达下降,srGAP2、γ-氨基丁酸及MCP-1与难治性癫痫发病密切相关,可能作为潜在治疗靶标。
