背景:程序性细胞死亡受体1(programmed death receptor-1,PD-1)在高糖环境下影响骨髓间充质干细胞成骨分化的作用机制尚不清楚。目的:探讨高糖环境中PD-1对大鼠骨髓间充质干细胞成骨分化的影响及其调控机制。方法:将大鼠骨髓间充质干细...背景:程序性细胞死亡受体1(programmed death receptor-1,PD-1)在高糖环境下影响骨髓间充质干细胞成骨分化的作用机制尚不清楚。目的:探讨高糖环境中PD-1对大鼠骨髓间充质干细胞成骨分化的影响及其调控机制。方法:将大鼠骨髓间充质干细胞随机分为正常糖组(5.6 mmol/L)、高糖组(30 mmol/L)、PD-1过表达组、PD-1过表达空载组、PD-1敲低组、PD-1敲低空载组、PI3K/AKT通路抑制剂组(PD-1敲低+5μmol/L LY294002)。通过在高糖培养基中培养大鼠骨髓间充质干细胞来模拟体外糖尿病环境,采用qRT-PCR检测大鼠骨髓间充质干细胞中PD-1及其配体PD-L1和成骨标志物Runx2、OSX的mRNA表达,采用碱性磷酸酶染色和茜素红S染色观察成骨分化能力,采用CCK-8检测细胞增殖情况,采用Western blot检测PD-1、PD-L1、p-PI3K、p-AKT的蛋白表达。结果与结论:①高糖组PD-1及PD-L1表达显著高于正常糖组,高糖组骨髓间充质干细胞的成骨分化能力较正常糖组显著下降;②敲低PD-1表达可以促进骨髓间充质干细胞的成骨分化、增加细胞增殖活性,同时激活PI3K/AKT通路;③加入PI3K/AKT通路抑制剂LY294002后,骨髓间充质干细胞成骨分化能力显著下降。结果表明:PD-1依赖于PI3K/AKT信号通路抑制高糖环境下大鼠骨髓间充质干细胞的成骨分化。展开更多
Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal sur...Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.展开更多
受体相互作用蛋白1(receptor interacting protein 1,RIP1)是一种在多个病理生理过程中发挥关键信号作用的蛋白激酶,其作为多种受体的下游信号分子,可介导细胞存活、炎症、凋亡等不同过程。RIP1与炎症反应、神经退行性疾病、免疫性疾病...受体相互作用蛋白1(receptor interacting protein 1,RIP1)是一种在多个病理生理过程中发挥关键信号作用的蛋白激酶,其作为多种受体的下游信号分子,可介导细胞存活、炎症、凋亡等不同过程。RIP1与炎症反应、神经退行性疾病、免疫性疾病和肿瘤性疾病等有较大相关性。RIP1既可促进肿瘤发生发展,也可抑制肿瘤活性,RIP1或可成为治疗肿瘤性疾病的重要突破口。本文主要就RIP1在细胞死亡中多重作用的具体机制及其与相关肿瘤的关系展开论述。展开更多
基金supported by the National Natural Science Foundation of China(Youth Science Fund Project),No.81901292(to GC)the National Key Research and Development Program of China,No.2021YFC2502100(to GC)the National Natural Science Foundation of China,No.82071183(to ZZ).
文摘Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.
文摘受体相互作用蛋白1(receptor interacting protein 1,RIP1)是一种在多个病理生理过程中发挥关键信号作用的蛋白激酶,其作为多种受体的下游信号分子,可介导细胞存活、炎症、凋亡等不同过程。RIP1与炎症反应、神经退行性疾病、免疫性疾病和肿瘤性疾病等有较大相关性。RIP1既可促进肿瘤发生发展,也可抑制肿瘤活性,RIP1或可成为治疗肿瘤性疾病的重要突破口。本文主要就RIP1在细胞死亡中多重作用的具体机制及其与相关肿瘤的关系展开论述。
