目的探讨Angptl3基因在大鼠高脂模型中各组织表达及其与血脂的关系。方法将60只清洁型SD大鼠随机分为4组:正常对照组、高脂血症组、糖尿病并发高脂血症组、IgA肾病并发高脂血症组。采用定量PCR(SYBR G reenⅠ)方法,检测以上4组大鼠脑、...目的探讨Angptl3基因在大鼠高脂模型中各组织表达及其与血脂的关系。方法将60只清洁型SD大鼠随机分为4组:正常对照组、高脂血症组、糖尿病并发高脂血症组、IgA肾病并发高脂血症组。采用定量PCR(SYBR G reenⅠ)方法,检测以上4组大鼠脑、肺、心、胃、肝、肾、脂肪等7种组织中Angptl3 mRNA的表达。结果Angptl3在4组大鼠的肝、肾组织中均有表达,其余5种组织中均未检测出有表达。其中肝表达量占总量的90%左右;并且随着表达总量的增加,肝表达量增加幅度较大。结论Angptl3在成年雄性SD大鼠肝、肾组织中特异表达,且此特异性不随血脂水平的改变而改变。展开更多
目的探讨血管生成素样蛋白3(angiopoietin-like protein 3,ANGPTL3)和基质金属蛋白酶(matrix metalloproteinases-2,MMP-2)及MMP-9在食管鳞状细胞癌中的表达及意义。方法应用免疫组织化学SP法检测52例食管鳞状细胞癌组织、癌旁组织和正...目的探讨血管生成素样蛋白3(angiopoietin-like protein 3,ANGPTL3)和基质金属蛋白酶(matrix metalloproteinases-2,MMP-2)及MMP-9在食管鳞状细胞癌中的表达及意义。方法应用免疫组织化学SP法检测52例食管鳞状细胞癌组织、癌旁组织和正常食管组织中ANGPTL3和MMP-2、MMP-9的表达。结果食管鳞状细胞癌组织中ANGPTL3、MMP-2和MMP-9的表达与癌旁组织和正常食管组织中的比较差异均有统计学意义(P<0.05)。结论 ANGPTL3和MMP-2、MMP-9在食管鳞状细胞癌中呈高表达,其联合检测有助于判断食管鳞状细胞癌生物学行为。展开更多
Three members of the angiopoietin-like(ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8-are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the int...Three members of the angiopoietin-like(ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8-are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the intravascular lipolysis of triglycerides present in some lipoprotein classes. This review focuses on the role of ANGPTL3 as emerged from the study of genetic variants of Angptl3 gene in mice and humans. Both loss of function genetic variants and inactivation of Angptl3 gene in mice are associated with a marked reduction of plasma levels of triglyceride and cholesterol and an increased activity of lipoprotein lipase and endothelial lipase. In humans with ANGPTL3 deficiency, caused by homozygous loss of function(LOF) variants of Angptl3 gene, the levels of all plasma lipoproteins are greatly reduced. This plasma lipid disorder referred to as familial combined hypolipidemia(FHBL2) does not appear to be associated with distinct pathological manifestations. Heterozygous carriers of LOF variants have reduced plasma levels of total cholesterol and triglycerides and are at lower risk of developing atherosclerotic cardiovascular disease, as compared to non-carriers. These observations have paved the way to the development of strategies to reduce the plasma level of atherogenic lipoproteins in man by the inactivation of ANGPTL3, using either a specific monoclonal antibody or anti-sense oligonucleotides.展开更多
Interleukin-1β(IL-1β)-induced signaling is one of the most important pathways in regulating inflammation and immunity.The assembly of the receptor complex,consisting of the ligand IL-1β,the IL-1 receptor(IL-1R)type...Interleukin-1β(IL-1β)-induced signaling is one of the most important pathways in regulating inflammation and immunity.The assembly of the receptor complex,consisting of the ligand IL-1β,the IL-1 receptor(IL-1R)type 1(IL1R1),and the IL-1R accessory protein(IL1RAP),initiates this signaling.However,how the IL1R1-associated complex is regulated remains elusive.Angiopoietin like 3(ANGPTL3),a key inhibitor of plasma triglyceride clearance,is mainly expressed in the liver and exists in both intracellular and extracellular secreted forms.Currently,ANGPTL3 has emerged as a highly promising drug target for hypertriglyceridemia and associated cardiovascular diseases.However,most studies have focused on the secreted form of ANGPTL3,while its intracellular role is still largely unknown.Here,we report that intracellular ANGPTL3 acts as a negative regulator of IL-1β-triggered signaling.Overexpression of ANGPTL3 inhibited IL-1β-induced NF-κB activation and the transcription of inflammatory genes in HepG2,THP1,and HEK293T cells,while knockdown or knockout of ANGPTL3 resulted in opposite effects.Mechanistically,ANGPTL3 interacted with IL1R1 and IL1RAP through its intracellular C-terminal fibrinogen-like domain and disrupted the assembly of the IL1R1-associated complex.Taken together,our study reveals a novel role for ANGPTL3 in inflammation,whereby it inhibits the physiological interaction between IL1R1 and IL1RAP to maintain immune tolerance and homeostasis in the liver.展开更多
文摘目的探讨Angptl3基因在大鼠高脂模型中各组织表达及其与血脂的关系。方法将60只清洁型SD大鼠随机分为4组:正常对照组、高脂血症组、糖尿病并发高脂血症组、IgA肾病并发高脂血症组。采用定量PCR(SYBR G reenⅠ)方法,检测以上4组大鼠脑、肺、心、胃、肝、肾、脂肪等7种组织中Angptl3 mRNA的表达。结果Angptl3在4组大鼠的肝、肾组织中均有表达,其余5种组织中均未检测出有表达。其中肝表达量占总量的90%左右;并且随着表达总量的增加,肝表达量增加幅度较大。结论Angptl3在成年雄性SD大鼠肝、肾组织中特异表达,且此特异性不随血脂水平的改变而改变。
文摘目的探讨血管生成素样蛋白3(angiopoietin-like protein 3,ANGPTL3)和基质金属蛋白酶(matrix metalloproteinases-2,MMP-2)及MMP-9在食管鳞状细胞癌中的表达及意义。方法应用免疫组织化学SP法检测52例食管鳞状细胞癌组织、癌旁组织和正常食管组织中ANGPTL3和MMP-2、MMP-9的表达。结果食管鳞状细胞癌组织中ANGPTL3、MMP-2和MMP-9的表达与癌旁组织和正常食管组织中的比较差异均有统计学意义(P<0.05)。结论 ANGPTL3和MMP-2、MMP-9在食管鳞状细胞癌中呈高表达,其联合检测有助于判断食管鳞状细胞癌生物学行为。
文摘Three members of the angiopoietin-like(ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8-are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the intravascular lipolysis of triglycerides present in some lipoprotein classes. This review focuses on the role of ANGPTL3 as emerged from the study of genetic variants of Angptl3 gene in mice and humans. Both loss of function genetic variants and inactivation of Angptl3 gene in mice are associated with a marked reduction of plasma levels of triglyceride and cholesterol and an increased activity of lipoprotein lipase and endothelial lipase. In humans with ANGPTL3 deficiency, caused by homozygous loss of function(LOF) variants of Angptl3 gene, the levels of all plasma lipoproteins are greatly reduced. This plasma lipid disorder referred to as familial combined hypolipidemia(FHBL2) does not appear to be associated with distinct pathological manifestations. Heterozygous carriers of LOF variants have reduced plasma levels of total cholesterol and triglycerides and are at lower risk of developing atherosclerotic cardiovascular disease, as compared to non-carriers. These observations have paved the way to the development of strategies to reduce the plasma level of atherogenic lipoproteins in man by the inactivation of ANGPTL3, using either a specific monoclonal antibody or anti-sense oligonucleotides.
基金supported by the Natural Science Foundation of China(31871411,31971066,and 82273838)the National Key R&D Program of China(2022YFA0806100)+1 种基金the Natural Science Foundation of Hubei Province(2021CFA004)the Analytical and Testing Center of Huazhong University of Science and Technology.
文摘Interleukin-1β(IL-1β)-induced signaling is one of the most important pathways in regulating inflammation and immunity.The assembly of the receptor complex,consisting of the ligand IL-1β,the IL-1 receptor(IL-1R)type 1(IL1R1),and the IL-1R accessory protein(IL1RAP),initiates this signaling.However,how the IL1R1-associated complex is regulated remains elusive.Angiopoietin like 3(ANGPTL3),a key inhibitor of plasma triglyceride clearance,is mainly expressed in the liver and exists in both intracellular and extracellular secreted forms.Currently,ANGPTL3 has emerged as a highly promising drug target for hypertriglyceridemia and associated cardiovascular diseases.However,most studies have focused on the secreted form of ANGPTL3,while its intracellular role is still largely unknown.Here,we report that intracellular ANGPTL3 acts as a negative regulator of IL-1β-triggered signaling.Overexpression of ANGPTL3 inhibited IL-1β-induced NF-κB activation and the transcription of inflammatory genes in HepG2,THP1,and HEK293T cells,while knockdown or knockout of ANGPTL3 resulted in opposite effects.Mechanistically,ANGPTL3 interacted with IL1R1 and IL1RAP through its intracellular C-terminal fibrinogen-like domain and disrupted the assembly of the IL1R1-associated complex.Taken together,our study reveals a novel role for ANGPTL3 in inflammation,whereby it inhibits the physiological interaction between IL1R1 and IL1RAP to maintain immune tolerance and homeostasis in the liver.
