Integrins are heterodimeric transmembrane receptors that mediate bidirectional interactions between the intracellular cytoskeletal array and the extracellularmatrix.These interactions are critical in tissue developmen...Integrins are heterodimeric transmembrane receptors that mediate bidirectional interactions between the intracellular cytoskeletal array and the extracellularmatrix.These interactions are critical in tissue development and function by regulating gene expression and sustaining tissue architecture.In humans,the integrin family is composed of 18 alpha(α)and 8 beta(β)subunits,constituting 24 distinctαβcombinations.Based on their structure and ligandbinding properties,only a subset of integrins,8 out of 24,recognizes the arginine-glycine-aspartate(RGD)tripeptide motif in the native ligand.One of the major RGD binding integrins is integrin alpha 8 beta 1(α8β1),a central Ras homolog gene familymemberA(RHOA)-dependentmodulator highly expressed in cells with contractile function.This review focuses on the recent advances regardingα8β1 function during organ development,with a particular interest in kidney and inner ear development.We alsodiscussα8β1’s role ininjury anddisease and its importance formesenchymal to epithelial transition during cancer development.Finally,we highlightα8β1’s importance for hearing function and its future use as a potential diagnostic and therapeutic tool for disease elimination.展开更多
目的:探讨精氨酸-甘氨酸-天冬氨酸(RGD)修饰对肿瘤抑素19肽(T-19)抗肝癌活性的影响,比较分析T-19及RGD修饰的T-19(RGD-T-19)对肝癌SK-Hep-1细胞增殖、侵袭和迁移能力的影响。方法:用Fmoc固相法合成T-19及RGD-T-19,用高效液相色谱仪和质...目的:探讨精氨酸-甘氨酸-天冬氨酸(RGD)修饰对肿瘤抑素19肽(T-19)抗肝癌活性的影响,比较分析T-19及RGD修饰的T-19(RGD-T-19)对肝癌SK-Hep-1细胞增殖、侵袭和迁移能力的影响。方法:用Fmoc固相法合成T-19及RGD-T-19,用高效液相色谱仪和质谱进行分离、鉴定。常规培养SK-Hep-1细胞,用0、50、100、150、200、250μg/mL的T-19及RGD-T-19分别处理细胞,分为0μg/mL(对照)组、50μg/mL组、100μg/mL组、150μg/mL组、200μg/mL组、250μg/mL组。CCK-8法、克隆形成实验、划痕愈合实验和Tanswell小室实验、WB法和q PCR法分别检测SK-Hep-1细胞的增殖、迁移、侵袭能力,以及环氧合酶-2(COX-2)、基质金属蛋白酶-2(MMP-2)、MMP-9、组织基质金属蛋白酶抑制剂-1(TIMP-1)、TIMP-2蛋白和MMP-1、MMP-2 mRNA的表达。结果:经质谱鉴定,用Fmoc固相法合成的T-19及RGD-T-19纯度高。T-19和RGD-T-19均能显著抑制SK-Hep-1细胞的增殖、迁移、侵袭能力,抑制COX-2蛋白、MMP-2和MMP-9蛋白及mRNA的表达、促进TIMP-1、TIMP-2蛋白的表达(P <0.05, P <0.01, P <0.001),RGD-T-19的抑制或促进效应均明显强于T-19(均P <0.05)。结论:利用Fmoc固相法合成了纯度高、活性好的T-19及RGD-T-19,两种肽均能抑制SK-Hep-1细胞增殖、侵袭和迁移能力,RGD-T-19作用明显强于T-19。展开更多
基金supported by NIH-NIDCD,5R01DC21070-0,and Creighton University’s Start-up funds to MZMs.Iman Ezzat was supported by the Department of Biomedical Sciences at Creighton University and the Bellucci Foundation pre-doctoral award.
文摘Integrins are heterodimeric transmembrane receptors that mediate bidirectional interactions between the intracellular cytoskeletal array and the extracellularmatrix.These interactions are critical in tissue development and function by regulating gene expression and sustaining tissue architecture.In humans,the integrin family is composed of 18 alpha(α)and 8 beta(β)subunits,constituting 24 distinctαβcombinations.Based on their structure and ligandbinding properties,only a subset of integrins,8 out of 24,recognizes the arginine-glycine-aspartate(RGD)tripeptide motif in the native ligand.One of the major RGD binding integrins is integrin alpha 8 beta 1(α8β1),a central Ras homolog gene familymemberA(RHOA)-dependentmodulator highly expressed in cells with contractile function.This review focuses on the recent advances regardingα8β1 function during organ development,with a particular interest in kidney and inner ear development.We alsodiscussα8β1’s role ininjury anddisease and its importance formesenchymal to epithelial transition during cancer development.Finally,we highlightα8β1’s importance for hearing function and its future use as a potential diagnostic and therapeutic tool for disease elimination.
文摘目的:探讨精氨酸-甘氨酸-天冬氨酸(RGD)修饰对肿瘤抑素19肽(T-19)抗肝癌活性的影响,比较分析T-19及RGD修饰的T-19(RGD-T-19)对肝癌SK-Hep-1细胞增殖、侵袭和迁移能力的影响。方法:用Fmoc固相法合成T-19及RGD-T-19,用高效液相色谱仪和质谱进行分离、鉴定。常规培养SK-Hep-1细胞,用0、50、100、150、200、250μg/mL的T-19及RGD-T-19分别处理细胞,分为0μg/mL(对照)组、50μg/mL组、100μg/mL组、150μg/mL组、200μg/mL组、250μg/mL组。CCK-8法、克隆形成实验、划痕愈合实验和Tanswell小室实验、WB法和q PCR法分别检测SK-Hep-1细胞的增殖、迁移、侵袭能力,以及环氧合酶-2(COX-2)、基质金属蛋白酶-2(MMP-2)、MMP-9、组织基质金属蛋白酶抑制剂-1(TIMP-1)、TIMP-2蛋白和MMP-1、MMP-2 mRNA的表达。结果:经质谱鉴定,用Fmoc固相法合成的T-19及RGD-T-19纯度高。T-19和RGD-T-19均能显著抑制SK-Hep-1细胞的增殖、迁移、侵袭能力,抑制COX-2蛋白、MMP-2和MMP-9蛋白及mRNA的表达、促进TIMP-1、TIMP-2蛋白的表达(P <0.05, P <0.01, P <0.001),RGD-T-19的抑制或促进效应均明显强于T-19(均P <0.05)。结论:利用Fmoc固相法合成了纯度高、活性好的T-19及RGD-T-19,两种肽均能抑制SK-Hep-1细胞增殖、侵袭和迁移能力,RGD-T-19作用明显强于T-19。
