Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous syst...Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous system (CNS) disorders, and involved in many aspects of neuronal functions including neurite outgrowth and retraction. In the adult CNS, the damaged neuron regeneration is very difficult due to the presence of myelin-associated axon growth inhibitors such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (Omgp), etc. The effects of these axon growth inhibitors are reversed by blocking the Rho/ROCK pathway 47 vitro, and the inhibition of Rho/ROCK pathway can promote axon regeneration and functional recovery in the injured CNS in viva In addition, the therapeutic effects of the Rho/ROCK inhibitors have also been demonstrated in some animal models and the Rho/ROCK pathway becomes an attractive target for the development of drugs for treating CNS disorders. In this review, we summarized on the effect of the Rho and the downstream factor ROCK in neural regeneration, and the potential therapeutic effect of Rho/ROCK inhibitors in the survival and axonal regeneration of retinal ganglion cell was also discussed.展开更多
神经可塑性是大脑在发育过程中产生的能够适应外界环境变化的能力,发生机制是神经元产生突触可塑性,通过突触与大脑其他部位的神经元相互作用,最终实现大脑功能的可塑性变化。神经可塑性是神经发生过程中一种重要的分子基础,对中枢神经...神经可塑性是大脑在发育过程中产生的能够适应外界环境变化的能力,发生机制是神经元产生突触可塑性,通过突触与大脑其他部位的神经元相互作用,最终实现大脑功能的可塑性变化。神经可塑性是神经发生过程中一种重要的分子基础,对中枢神经系统疾病的治疗具有重要意义。Rho/ROCK(Rho GTPase/Rho-associated protein kinase)信号通路是目前研究最为广泛的信号通路之一,它在神经发育和突触可塑性中都发挥了重要作用。本文就Rho/ROCK信号通路在神经可塑性中的作用及相关研究进展进行综述。展开更多
Mesenchymal stem cell （MSC）-based treatments have shown promise for improving tendon healing and repair. MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical st...Mesenchymal stem cell （MSC）-based treatments have shown promise for improving tendon healing and repair. MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical stimuli, including into tenocytes. Cell elongation and cytoskeletal tension have been shown to be instrumental to the process of MSC differentiation. Previous studies have shown that inhibition of stress fiber formation leads MSCs to default toward an adipogenic lineage, which suggests that stress fibers are required for MSCs to sense the environmental factors that can induce differentiation into tenocytes. As the Rho/ROCK signal transduction pathway plays a critical role in both stress fiber formation and in cell sensation, we examined whether the activation of this pathway was required when inducing MSC tendon differentiation using rope-like silk scaffolds. To accomplish this, we employed a loss-of-function approach by knocking out ROCK, actin and myosin （two other components of the pathway） using the specific inhibitors Y-27632, Latrunculin A and blebbistatin, respectively. We demonstrated that independently disrupting the cytoskeleton and the Rho/ ROCK pathway abolished the expression of tendon differentiation markers and led to a loss of spindle morphology. Together, these studies suggest that the tension that is generated by MSC elongation is essential for MSC teno-differentiation and that the Rho/ROCK pathway is a critical mediator of tendon differentiation on rope-like silk scaffolds.展开更多
RhoA is a small GTPase protein.Its downstream effector protein Rho kinase(ROCK)regulates a variety of cell functions,including cell growth,gene expression and cytoskeleton recombination.Studies have demonstrated that ...RhoA is a small GTPase protein.Its downstream effector protein Rho kinase(ROCK)regulates a variety of cell functions,including cell growth,gene expression and cytoskeleton recombination.Studies have demonstrated that this pathway plays an important pathophysiological role in diabetic nephropathy and other complications,hypertension,stroke,tumor,osteoarthritis,acute lung injury and other diseases.The occurrence and development of diabetes-related disease is closely related to the activation or up-regulation of RhoA/ROCK pathway.As a key target of drug development,ROCK inhibitors have been widely concerned by scholars.This article reviews the relationship between RhoA/ROCK pathway and diabetesrelated disease,and offers a new and effective strategy for the prevention and treatment of this series of diseases.展开更多
基金Supported by National Nature Science Foundation of China (No.81070728)Shanghai "Science and Technology Innovation Action Plan" Basic Research Key Project,China (No.11JC1407700 and 11 JC1407701)+1 种基金Shanghai Nature Science Foundation, China (No.08ZR1413900)Shanghai Leading Academic Discipline Project, China(No.S30205)
文摘Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous system (CNS) disorders, and involved in many aspects of neuronal functions including neurite outgrowth and retraction. In the adult CNS, the damaged neuron regeneration is very difficult due to the presence of myelin-associated axon growth inhibitors such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (Omgp), etc. The effects of these axon growth inhibitors are reversed by blocking the Rho/ROCK pathway 47 vitro, and the inhibition of Rho/ROCK pathway can promote axon regeneration and functional recovery in the injured CNS in viva In addition, the therapeutic effects of the Rho/ROCK inhibitors have also been demonstrated in some animal models and the Rho/ROCK pathway becomes an attractive target for the development of drugs for treating CNS disorders. In this review, we summarized on the effect of the Rho and the downstream factor ROCK in neural regeneration, and the potential therapeutic effect of Rho/ROCK inhibitors in the survival and axonal regeneration of retinal ganglion cell was also discussed.
文摘神经可塑性是大脑在发育过程中产生的能够适应外界环境变化的能力,发生机制是神经元产生突触可塑性,通过突触与大脑其他部位的神经元相互作用,最终实现大脑功能的可塑性变化。神经可塑性是神经发生过程中一种重要的分子基础,对中枢神经系统疾病的治疗具有重要意义。Rho/ROCK(Rho GTPase/Rho-associated protein kinase)信号通路是目前研究最为广泛的信号通路之一,它在神经发育和突触可塑性中都发挥了重要作用。本文就Rho/ROCK信号通路在神经可塑性中的作用及相关研究进展进行综述。
文摘Mesenchymal stem cell （MSC）-based treatments have shown promise for improving tendon healing and repair. MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical stimuli, including into tenocytes. Cell elongation and cytoskeletal tension have been shown to be instrumental to the process of MSC differentiation. Previous studies have shown that inhibition of stress fiber formation leads MSCs to default toward an adipogenic lineage, which suggests that stress fibers are required for MSCs to sense the environmental factors that can induce differentiation into tenocytes. As the Rho/ROCK signal transduction pathway plays a critical role in both stress fiber formation and in cell sensation, we examined whether the activation of this pathway was required when inducing MSC tendon differentiation using rope-like silk scaffolds. To accomplish this, we employed a loss-of-function approach by knocking out ROCK, actin and myosin （two other components of the pathway） using the specific inhibitors Y-27632, Latrunculin A and blebbistatin, respectively. We demonstrated that independently disrupting the cytoskeleton and the Rho/ ROCK pathway abolished the expression of tendon differentiation markers and led to a loss of spindle morphology. Together, these studies suggest that the tension that is generated by MSC elongation is essential for MSC teno-differentiation and that the Rho/ROCK pathway is a critical mediator of tendon differentiation on rope-like silk scaffolds.
基金National Natural Science Foundation of China(No.81660148)Innovation and Entrepreneurship Project of Science and Technology Bureau of Chengguan District of Lanzhou City(No.2018HFZ0068)Hospital cultivation Program of Gansu Provincial people's Hospital(No.19SYPYB-4).
文摘RhoA is a small GTPase protein.Its downstream effector protein Rho kinase(ROCK)regulates a variety of cell functions,including cell growth,gene expression and cytoskeleton recombination.Studies have demonstrated that this pathway plays an important pathophysiological role in diabetic nephropathy and other complications,hypertension,stroke,tumor,osteoarthritis,acute lung injury and other diseases.The occurrence and development of diabetes-related disease is closely related to the activation or up-regulation of RhoA/ROCK pathway.As a key target of drug development,ROCK inhibitors have been widely concerned by scholars.This article reviews the relationship between RhoA/ROCK pathway and diabetesrelated disease,and offers a new and effective strategy for the prevention and treatment of this series of diseases.
