目的:探讨XMU-MP-1(Xiamen University-inhibitor of mammalian sterile 20-like kinase protein 1)对氧糖剥夺(OGD)损伤后小胶质细胞M1/M2极化平衡的调节作用。方法采用OGD法诱导BV2细胞损伤。实验分为6组:对照组、模型组、MST1/2 siRN...目的:探讨XMU-MP-1(Xiamen University-inhibitor of mammalian sterile 20-like kinase protein 1)对氧糖剥夺(OGD)损伤后小胶质细胞M1/M2极化平衡的调节作用。方法采用OGD法诱导BV2细胞损伤。实验分为6组:对照组、模型组、MST1/2 siRNA组和低、中、高剂量实验组(分别给予1.25、5.0和20.0μg·mL^(-1) XMU-MP-1)。采用MTT法测细胞活力,ELISA测细胞上清液中TNF-α、IL-6和IL-1β表达,qRT-PCR测M1和M2标志物的mRNA表达,流式细胞术测CD206表达,蛋白印迹法测MST1、LATS1和YAP蛋白表达。结果与模型组相比,XMU-MP-1抑制BV2细胞增殖,显著降低TNF-α、IL-6和IL-1β的表达水平,下调MCP-1、IL-6、TNF-α和i NOS mRNA的表达,上调CD206、IL-10、TGF-β、IL-10和YM1 mRNA表达,降低MST1和LAST 1蛋白表达,上调YAP和CD206表达。结论XMU-MP-1通过调控MST1/2的磷酸化,调节OGD损伤后的BV2细胞M1/M2极化平衡,为神经炎症靶点药物研发提供理论基础。展开更多
砷是一种自然环境中广泛存在的非金属元素[1]。人类在自然环境和工业活动中长期接触受砷污染的水、空气和食物而中毒,造成组织器官损伤、甚至癌变。此外,砷引起神经系统损害也受到人们越来越多的关注[2]。但目前砷引起神经损伤的具体机...砷是一种自然环境中广泛存在的非金属元素[1]。人类在自然环境和工业活动中长期接触受砷污染的水、空气和食物而中毒,造成组织器官损伤、甚至癌变。此外,砷引起神经系统损害也受到人们越来越多的关注[2]。但目前砷引起神经损伤的具体机制仍不是十分明确。Hippo信号通路是一条在进化上高度保守的激酶级联信号通路,主要控制器官大小、组织稳态和组织再生[3]。本课题组已经证实,NaAsO_(2)可通过激活Hippo信号通路,诱导PC12细胞凋亡。突触后致密蛋白95(post synaptic density protein,PSD95)、突触素蛋白(synaptophysin,SYN)作为神经突触功能相关蛋白,其表达和缺失在神经系统疾病中十分重要[4]。因此,本实验在前期研究的基础上探讨Hippo通路是否参与NaAsO_(2)对PC12细胞活性、形态以及PSD95、SYN神经突触相关蛋白表达的影响。展开更多
The Hippo signaling pathway has been established as a key regulator of organ size control,tumor suppression,and tissue regeneration in multiple organisms.Recently,emerging evidence has indicated that Hippo signaling m...The Hippo signaling pathway has been established as a key regulator of organ size control,tumor suppression,and tissue regeneration in multiple organisms.Recently,emerging evidence has indicated that Hippo signaling might play an important role in regulating the immune system in both Drosophila and mammals.In particular,patients bearing a loss-of-function mutation of MST1 are reported to have an autosomal recessive primary immunodeficiency syndrome.MST1/2 kinases,the mammalian orthologs of Drosophila Hippo,may activate the non-canonical Hippo signaling pathway via MOB1A/B and/or NDR1/2 or cross-talk with other essential signaling pathways to regulate both innate and adaptive immunity.In this review,we present and discuss recent findings of cellular mechanisms/functions of Hippo signaling in the innate immunity in Drosophila and in mammals,T cell immunity,as well as the implications of Hippo signaling for tumor immunity.展开更多
The Hippo pathway plays a crucial role in controlling organ size by inhibiting cell proliferation and promoting cell death.Recent findings implicate that this pathway is involved in the process of intestinal regenerat...The Hippo pathway plays a crucial role in controlling organ size by inhibiting cell proliferation and promoting cell death.Recent findings implicate that this pathway is involved in the process of intestinal regeneration and tumorigenesis.Here we summarize current studies for the function of the Hippo signaling pathway in intestinal homeostasis,regeneration and tumorigenesis,and the crosstalk between the Hippo signaling pathway and other major signaling pathways,i.e.Wnt,Notch and Jak/Stat signaling pathways in intestinal compartment.展开更多
Cardiovascular diseases(CVDs)and metabolic disorders are major components of noncommunicable diseases,causing an enormous health and economic burden worldwide.There are common risk factors and developmental mechanisms...Cardiovascular diseases(CVDs)and metabolic disorders are major components of noncommunicable diseases,causing an enormous health and economic burden worldwide.There are common risk factors and developmental mechanisms among them,indicating the far-reaching significance in exploring the corresponding therapeutic targets.MST1/2 kinases are well-established proapoptotic effectors that also bidirectionally regulate autophagic activity.Recent studies have demonstrated that MST1/2 influence the outcome of cardiovascular and metabolic diseases by regulating immune inflammation.In addition,drug development against them is in full swing.In this review,we mainly describe the roles and mechanisms of MST1/2 in apoptosis and autophagy in cardiovascular and metabolic events as well as emphasis on the existing evidence for their involvement in immune inflammation.Moreover,we summarize the latest progress of pharmacotherapy targeting MST1/2 and propose a new mode of drug combination therapy,which may be beneficial to seek more effective strategies to prevent and treat CVDs and metabolic disorders.展开更多
文摘目的:探讨XMU-MP-1(Xiamen University-inhibitor of mammalian sterile 20-like kinase protein 1)对氧糖剥夺(OGD)损伤后小胶质细胞M1/M2极化平衡的调节作用。方法采用OGD法诱导BV2细胞损伤。实验分为6组:对照组、模型组、MST1/2 siRNA组和低、中、高剂量实验组(分别给予1.25、5.0和20.0μg·mL^(-1) XMU-MP-1)。采用MTT法测细胞活力,ELISA测细胞上清液中TNF-α、IL-6和IL-1β表达,qRT-PCR测M1和M2标志物的mRNA表达,流式细胞术测CD206表达,蛋白印迹法测MST1、LATS1和YAP蛋白表达。结果与模型组相比,XMU-MP-1抑制BV2细胞增殖,显著降低TNF-α、IL-6和IL-1β的表达水平,下调MCP-1、IL-6、TNF-α和i NOS mRNA的表达,上调CD206、IL-10、TGF-β、IL-10和YM1 mRNA表达,降低MST1和LAST 1蛋白表达,上调YAP和CD206表达。结论XMU-MP-1通过调控MST1/2的磷酸化,调节OGD损伤后的BV2细胞M1/M2极化平衡,为神经炎症靶点药物研发提供理论基础。
文摘砷是一种自然环境中广泛存在的非金属元素[1]。人类在自然环境和工业活动中长期接触受砷污染的水、空气和食物而中毒,造成组织器官损伤、甚至癌变。此外,砷引起神经系统损害也受到人们越来越多的关注[2]。但目前砷引起神经损伤的具体机制仍不是十分明确。Hippo信号通路是一条在进化上高度保守的激酶级联信号通路,主要控制器官大小、组织稳态和组织再生[3]。本课题组已经证实,NaAsO_(2)可通过激活Hippo信号通路,诱导PC12细胞凋亡。突触后致密蛋白95(post synaptic density protein,PSD95)、突触素蛋白(synaptophysin,SYN)作为神经突触功能相关蛋白,其表达和缺失在神经系统疾病中十分重要[4]。因此,本实验在前期研究的基础上探讨Hippo通路是否参与NaAsO_(2)对PC12细胞活性、形态以及PSD95、SYN神经突触相关蛋白表达的影响。
基金This work was supported by grants from National Key R&D Program of China(2017YFA0504502 to D.Z.and L.C.,2015CB910502 to L.C.)The National Natural Science Foundation of China(U1405225 to L.C.,31625010,81790254,and U1505224 to D.Z.,81472229 to L.H.,81302529 to X.L.)the Fundamental Research Funds for the Central Universities of China-Xiamen University(20720180047 to L.C.,20720160071 to D.Z.,and 20720160054 to L.H.).
文摘The Hippo signaling pathway has been established as a key regulator of organ size control,tumor suppression,and tissue regeneration in multiple organisms.Recently,emerging evidence has indicated that Hippo signaling might play an important role in regulating the immune system in both Drosophila and mammals.In particular,patients bearing a loss-of-function mutation of MST1 are reported to have an autosomal recessive primary immunodeficiency syndrome.MST1/2 kinases,the mammalian orthologs of Drosophila Hippo,may activate the non-canonical Hippo signaling pathway via MOB1A/B and/or NDR1/2 or cross-talk with other essential signaling pathways to regulate both innate and adaptive immunity.In this review,we present and discuss recent findings of cellular mechanisms/functions of Hippo signaling in the innate immunity in Drosophila and in mammals,T cell immunity,as well as the implications of Hippo signaling for tumor immunity.
基金supported by grants from the China’s 1000 Young Talents Program,the 111 Project of The Ministration of Education of China(No.B06016)the Fundamental Research Funds for the Central Universities of China(No.2010111079)+1 种基金National Natural Science Foundation of China(Grant No.81101503)and Natural Science Foundation of Fujian(No.2011J05096)supported by the RO1 awards CA136567(JA),DK17776(JA)and institutional funds.The authors have no financial conflicts to disclose.
文摘The Hippo pathway plays a crucial role in controlling organ size by inhibiting cell proliferation and promoting cell death.Recent findings implicate that this pathway is involved in the process of intestinal regeneration and tumorigenesis.Here we summarize current studies for the function of the Hippo signaling pathway in intestinal homeostasis,regeneration and tumorigenesis,and the crosstalk between the Hippo signaling pathway and other major signaling pathways,i.e.Wnt,Notch and Jak/Stat signaling pathways in intestinal compartment.
基金grants from the National Natural Science Foundation of China(Nos.81770327 and 81100173)Jiangsu Province Health Care Development Special Fund(M2022038,China)。
文摘Cardiovascular diseases(CVDs)and metabolic disorders are major components of noncommunicable diseases,causing an enormous health and economic burden worldwide.There are common risk factors and developmental mechanisms among them,indicating the far-reaching significance in exploring the corresponding therapeutic targets.MST1/2 kinases are well-established proapoptotic effectors that also bidirectionally regulate autophagic activity.Recent studies have demonstrated that MST1/2 influence the outcome of cardiovascular and metabolic diseases by regulating immune inflammation.In addition,drug development against them is in full swing.In this review,we mainly describe the roles and mechanisms of MST1/2 in apoptosis and autophagy in cardiovascular and metabolic events as well as emphasis on the existing evidence for their involvement in immune inflammation.Moreover,we summarize the latest progress of pharmacotherapy targeting MST1/2 and propose a new mode of drug combination therapy,which may be beneficial to seek more effective strategies to prevent and treat CVDs and metabolic disorders.
