Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-e...Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction.However,the mechanisms involved remain unclear.In this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming phenotypes.The expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury.In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between them.We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway.This,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways.In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function recovery.Overall,Gas6 may play a role in the treatment of spinal cord injury.It can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.展开更多
目的:研究信号转导和转录激活因子1(signal transducer and activator of transcription 1,STAT1)对癌症相关生长抑制特异性基因6(growth arrest specific 6,Gas6)的影响及其机制。方法:应用数据库预测乳腺癌的基因聚类分析结果,并预测G...目的:研究信号转导和转录激活因子1(signal transducer and activator of transcription 1,STAT1)对癌症相关生长抑制特异性基因6(growth arrest specific 6,Gas6)的影响及其机制。方法:应用数据库预测乳腺癌的基因聚类分析结果,并预测Gas6与STAT1在多种癌症中的相关性;通过染色质免疫沉淀(chromatin immunoprecipitation,ChIP)实验检测STAT1是否可与Gas6启动子结合,应用数据库预测STAT1在Gas6启动子上的结合位点并突变其关键碱基,通过双萤光素酶报告基因实验检测结合位点突变对Gas6启动子活性的影响,同时分别检测敲低或过表达STAT1对Gas6启动子和突变的Gas6启动子活性的影响;通过实时荧光定量PCR技术和蛋白质免疫印迹技术分别检测敲低或过表达STAT1对Gas6 mRNA及蛋白表达的影响。结果:Gas6基因在乳腺癌中高表达;Gas6与STAT1在多种癌症中有正相关趋势;Gas6启动子序列包含STAT1的结合位点,并且有调控Gas6启动子活性的功能性结合位点。转录因子STAT1可在转录水平对癌症相关基因Gas6进行正向调控。结论:癌症相关基因Gas6是转录因子STAT1的直接靶基因。展开更多
目的探讨新据维、汉民族乳腺良恶性组织中Anexelekto（Axl）及其配体生长停滞特异性基因6蛋白（Growtharrest specific gene6，Gas6）的表达及其临床病胖意义。方法选择2006年1月-2007年1月新疆医科大学附属肿瘤医院乳腺外科收治的Ⅰ～...目的探讨新据维、汉民族乳腺良恶性组织中Anexelekto（Axl）及其配体生长停滞特异性基因6蛋白（Growtharrest specific gene6，Gas6）的表达及其临床病胖意义。方法选择2006年1月-2007年1月新疆医科大学附属肿瘤医院乳腺外科收治的Ⅰ～Ⅲ期可手术且临床及病理资料完整的乳腺癌患者252例及乳腺良性增生21例，用免疫组化PV-9000法检测Axl及其配体Gas6的表达情况，分析其表达情况与临床病理指标的关系。结果作乳腺痛组织中Axl蛋白的阳性表达率为63．5％，明显高于正常对照组织的28．6％，差异有统计学意义（P〈50．05）；Gas6在癌组织的阳性表达率为47．6％，明显高于正常对照组织的23．8％，差异有统计学意义（P〈0.05）。不同民族、不同年龄组、不同病理类型及不同分子分型组间Axl和Gas6蛋白的阳性表达率差异无统计学意义（P〉0．05）；Axl和Gas6蛋白的刚性表达率随着肿瘤T分期及组织学分级的增高而增高，差异均具有统计意义（P〈0.05）；红淋巴结有转移纰的Axl和Gas6蛋白的阳性表达率分别为70．4％、56．3％，明显高于淋巴结无转移组的50．9％和36．4％，差异有统计学意义（P〈0．05）；在脉管有浸润组的Axl和Gas6蛋白的阳性表达率也明显高于无浸润组，差异有统计学意义（P〈0．05）。结论新疆维、汉民族良恶性病变组织中Axl、Gas6的表达水平与肿瘤的T分期、纰织学分级、腋窝淋巴结转移及脉管浸润有密切关系。展开更多
基金supported by the National Natural Science Foundation of China, Nos.81971151 (to YW), 82102528 (to XL), 82102583 (to LW)the Natural Science Foundation of Guangdong Province, China, Nos.2020A1515010265 (to YW), 2020A1515110679 (to XL), and 2021A1515010358 (to XL)
文摘Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction.However,the mechanisms involved remain unclear.In this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming phenotypes.The expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury.In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between them.We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway.This,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways.In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function recovery.Overall,Gas6 may play a role in the treatment of spinal cord injury.It can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.
文摘目的:研究信号转导和转录激活因子1(signal transducer and activator of transcription 1,STAT1)对癌症相关生长抑制特异性基因6(growth arrest specific 6,Gas6)的影响及其机制。方法:应用数据库预测乳腺癌的基因聚类分析结果,并预测Gas6与STAT1在多种癌症中的相关性;通过染色质免疫沉淀(chromatin immunoprecipitation,ChIP)实验检测STAT1是否可与Gas6启动子结合,应用数据库预测STAT1在Gas6启动子上的结合位点并突变其关键碱基,通过双萤光素酶报告基因实验检测结合位点突变对Gas6启动子活性的影响,同时分别检测敲低或过表达STAT1对Gas6启动子和突变的Gas6启动子活性的影响;通过实时荧光定量PCR技术和蛋白质免疫印迹技术分别检测敲低或过表达STAT1对Gas6 mRNA及蛋白表达的影响。结果:Gas6基因在乳腺癌中高表达;Gas6与STAT1在多种癌症中有正相关趋势;Gas6启动子序列包含STAT1的结合位点,并且有调控Gas6启动子活性的功能性结合位点。转录因子STAT1可在转录水平对癌症相关基因Gas6进行正向调控。结论:癌症相关基因Gas6是转录因子STAT1的直接靶基因。
文摘目的探讨新据维、汉民族乳腺良恶性组织中Anexelekto（Axl）及其配体生长停滞特异性基因6蛋白（Growtharrest specific gene6，Gas6）的表达及其临床病胖意义。方法选择2006年1月-2007年1月新疆医科大学附属肿瘤医院乳腺外科收治的Ⅰ～Ⅲ期可手术且临床及病理资料完整的乳腺癌患者252例及乳腺良性增生21例，用免疫组化PV-9000法检测Axl及其配体Gas6的表达情况，分析其表达情况与临床病理指标的关系。结果作乳腺痛组织中Axl蛋白的阳性表达率为63．5％，明显高于正常对照组织的28．6％，差异有统计学意义（P〈50．05）；Gas6在癌组织的阳性表达率为47．6％，明显高于正常对照组织的23．8％，差异有统计学意义（P〈0.05）。不同民族、不同年龄组、不同病理类型及不同分子分型组间Axl和Gas6蛋白的阳性表达率差异无统计学意义（P〉0．05）；Axl和Gas6蛋白的刚性表达率随着肿瘤T分期及组织学分级的增高而增高，差异均具有统计意义（P〈0.05）；红淋巴结有转移纰的Axl和Gas6蛋白的阳性表达率分别为70．4％、56．3％，明显高于淋巴结无转移组的50．9％和36．4％，差异有统计学意义（P〈0．05）；在脉管有浸润组的Axl和Gas6蛋白的阳性表达率也明显高于无浸润组，差异有统计学意义（P〈0．05）。结论新疆维、汉民族良恶性病变组织中Axl、Gas6的表达水平与肿瘤的T分期、纰织学分级、腋窝淋巴结转移及脉管浸润有密切关系。
