Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeut...Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.展开更多
目的探讨轴抑制因子(AXIN)通过β-catenin调控MMP7、MMP9对淋巴瘤细胞侵袭迁移能力的影响。方法用RT-PCR和Western blot法观察多株淋巴瘤细胞株里AXIN、β-catenin、MMP7、MMP9的表达情况;选取AXIN相对低表达的淋巴瘤细胞分组瞬时转染p ...目的探讨轴抑制因子(AXIN)通过β-catenin调控MMP7、MMP9对淋巴瘤细胞侵袭迁移能力的影响。方法用RT-PCR和Western blot法观察多株淋巴瘤细胞株里AXIN、β-catenin、MMP7、MMP9的表达情况;选取AXIN相对低表达的淋巴瘤细胞分组瞬时转染p CMV5-HA-Axin和pc DNA5-His-β-catenin质粒,采用RT-PCR和Western blot法观察其细胞中β-catenin、MMP7、MMP9 m RNA及蛋白表达变化;构建稳定高表达AXIN的淋巴瘤细胞后,分组瞬时转染AXIN-sh RNA和β-catenin-sh RNA后观察β-catenin、MMP7、MMP9 m RNA及蛋白变化;采用Transwell侵袭实验观察空白处理对照组、稳定高表达AXIN组、干扰AXIN的稳定高表达AXIN组细胞侵袭和迁移能力变化。结果多株淋巴瘤细胞株中AXIN与β-catenin、MMP7、MMP9表达呈负相关;选用AXIN相对低表达的人恶性B淋巴瘤细胞株Raji,过表达AXIN后发现AXIN升高后,β-catenin、MMP7、MMP9的蛋白表达降低,MMP7、MMP9、β-catenin m RNA未变化;当过表达β-catenin后发现MMP7、MMP9 m RNA和蛋白表达升高;另外,稳定高表达AXIN的细胞中干扰AXIN,β-catenin、MMP7、MMP9蛋白表达升高,MMP7、MMP9、β-catenin m RNA未变化;稳定高表达AXIN的细胞中干扰β-catenin,MMP7、MMP9表达降低;证实AXIN通过β-catenin调控MMP7、MMP9影响淋巴瘤细胞的侵袭和迁移。结论在淋巴瘤细胞中升高AXIN可引起β-catenin表达下降,进而MMP7、MMP9表达下降,抑制淋巴瘤细胞的侵袭和迁移。展开更多
目的:观察慢病毒介导的NIBP(NIK and IKKβbinding protein)基因转染结肠癌细胞株HT29后,细胞迁移能力以及细胞内p65、MMP2、MMP9 m RNA和蛋白表达的变化。方法:分为未经转染的HT29细胞(HT29组)、转染空载的HT29细胞(HT29-NC组)和转染N...目的:观察慢病毒介导的NIBP(NIK and IKKβbinding protein)基因转染结肠癌细胞株HT29后,细胞迁移能力以及细胞内p65、MMP2、MMP9 m RNA和蛋白表达的变化。方法:分为未经转染的HT29细胞(HT29组)、转染空载的HT29细胞(HT29-NC组)和转染NIBP的HT29细胞(HT29-NIBP稳转组)。采用Transwell试验检测细胞迁移能力;Q-PCR法检测NIBP、p65、MMP2、MMP9的m RNA表达;Western Blot法检测NIBP、p65、磷酸化p65(p-p65)的蛋白表达;ELISA法检测MMP2、MMP9的分泌。结果:高表达NIBP能增强结肠癌细胞株HT29的迁移能力,并主要通过增加p-p65从而促进MMP2、MMP9 m RNA及蛋白表达(P<0.05)。结论:NIBP可能通过激活NF-κB信号通路促进结肠癌细胞分泌MMP-2、MMP-9,从而促进结肠癌细胞的侵袭转移。展开更多
文摘Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.
文摘目的探讨轴抑制因子(AXIN)通过β-catenin调控MMP7、MMP9对淋巴瘤细胞侵袭迁移能力的影响。方法用RT-PCR和Western blot法观察多株淋巴瘤细胞株里AXIN、β-catenin、MMP7、MMP9的表达情况;选取AXIN相对低表达的淋巴瘤细胞分组瞬时转染p CMV5-HA-Axin和pc DNA5-His-β-catenin质粒,采用RT-PCR和Western blot法观察其细胞中β-catenin、MMP7、MMP9 m RNA及蛋白表达变化;构建稳定高表达AXIN的淋巴瘤细胞后,分组瞬时转染AXIN-sh RNA和β-catenin-sh RNA后观察β-catenin、MMP7、MMP9 m RNA及蛋白变化;采用Transwell侵袭实验观察空白处理对照组、稳定高表达AXIN组、干扰AXIN的稳定高表达AXIN组细胞侵袭和迁移能力变化。结果多株淋巴瘤细胞株中AXIN与β-catenin、MMP7、MMP9表达呈负相关;选用AXIN相对低表达的人恶性B淋巴瘤细胞株Raji,过表达AXIN后发现AXIN升高后,β-catenin、MMP7、MMP9的蛋白表达降低,MMP7、MMP9、β-catenin m RNA未变化;当过表达β-catenin后发现MMP7、MMP9 m RNA和蛋白表达升高;另外,稳定高表达AXIN的细胞中干扰AXIN,β-catenin、MMP7、MMP9蛋白表达升高,MMP7、MMP9、β-catenin m RNA未变化;稳定高表达AXIN的细胞中干扰β-catenin,MMP7、MMP9表达降低;证实AXIN通过β-catenin调控MMP7、MMP9影响淋巴瘤细胞的侵袭和迁移。结论在淋巴瘤细胞中升高AXIN可引起β-catenin表达下降,进而MMP7、MMP9表达下降,抑制淋巴瘤细胞的侵袭和迁移。
文摘目的:观察慢病毒介导的NIBP(NIK and IKKβbinding protein)基因转染结肠癌细胞株HT29后,细胞迁移能力以及细胞内p65、MMP2、MMP9 m RNA和蛋白表达的变化。方法:分为未经转染的HT29细胞(HT29组)、转染空载的HT29细胞(HT29-NC组)和转染NIBP的HT29细胞(HT29-NIBP稳转组)。采用Transwell试验检测细胞迁移能力;Q-PCR法检测NIBP、p65、MMP2、MMP9的m RNA表达;Western Blot法检测NIBP、p65、磷酸化p65(p-p65)的蛋白表达;ELISA法检测MMP2、MMP9的分泌。结果:高表达NIBP能增强结肠癌细胞株HT29的迁移能力,并主要通过增加p-p65从而促进MMP2、MMP9 m RNA及蛋白表达(P<0.05)。结论:NIBP可能通过激活NF-κB信号通路促进结肠癌细胞分泌MMP-2、MMP-9,从而促进结肠癌细胞的侵袭转移。
