Abstract：
OBJECTIVE: Miniature pigs are considered ideal organ donors for xenotransplantation in humans, but the mechanism underlying their dwarfism remains to be elucidated. IGF-1R is a crucial factor in body size formation in mammals, including skeletal muscle formation and development. The extracellular domain (ECD) binds to the ligand, a phenomenon that results in the activation of downstream pathways.
METHODS: In this study, the coding sequences of two IGF-1R ECD haplotypes of the large Landrace (LP) pig and the small Bama Xiang (BM) pig were cloned into pcDNA3.1 vectors to generate pcDNA3.1-LP and pcDNA3.1-BM. The two recombinant vectors were then transfected into skeletal muscle cells.
RESULTS: IGF-1R transcript was found to be expressed at higher levels in the pcDNA3.1-LP group than in the pcDNA3.1-BM group. The IGF-1R ECD from LP promoted cell proliferation and CyclinD1 expression, and promoted the phosphorylation of protein kinase B (to yield p-AKT). Moreover, the IGF-1R ECD from LP increased cell differentiation and the expression of myogenic determination factor (MyoD).
CONCLUSIONS: Our data indicated that the IGF-1R ECD haplotypes between pig breeds with different body sizes affect IGF-1R expression, in turn affecting the proliferation and differentiation of skeletal muscle cells by activating downstream signalling pathways.
METHODS: In this study, the coding sequences of two IGF-1R ECD haplotypes of the large Landrace (LP) pig and the small Bama Xiang (BM) pig were cloned into pcDNA3.1 vectors to generate pcDNA3.1-LP and pcDNA3.1-BM. The two recombinant vectors were then transfected into skeletal muscle cells.
RESULTS: IGF-1R transcript was found to be expressed at higher levels in the pcDNA3.1-LP group than in the pcDNA3.1-BM group. The IGF-1R ECD from LP promoted cell proliferation and CyclinD1 expression, and promoted the phosphorylation of protein kinase B (to yield p-AKT). Moreover, the IGF-1R ECD from LP increased cell differentiation and the expression of myogenic determination factor (MyoD).
CONCLUSIONS: Our data indicated that the IGF-1R ECD haplotypes between pig breeds with different body sizes affect IGF-1R expression, in turn affecting the proliferation and differentiation of skeletal muscle cells by activating downstream signalling pathways.
摘要：
目的：小型猪被认为是人类异种移植的理想器官供体，但其侏儒症背后的机制仍有待阐明。IGF-1R是哺乳动物体型形成的关键因素，包括骨骼肌的形成和发育。细胞外结构域（ECD）与配体结合，导致下游途径激活的现象。
方法：在本研究中，将大型长白猪（LP）和小型巴马香（BM）猪的两种IGF-1RECD单倍型的编码序列克隆到pcDNA3.1载体中，以生成pcDNA3.1-LP和pcDNA3.1-BM。然后将两种重组载体转染到骨骼肌细胞中。
结果：发现IGF-1R转录本在pcDNA3.1-LP组中的表达水平高于pcDNA3.1-BM组。来自LP的IGF-1RECD促进细胞增殖和CyclinD1表达,并促进蛋白激酶B的磷酸化（产生p-AKT）。此外，来自LP的IGF-1RECD增加了细胞分化和成肌决定因子（MyoD）的表达。
结论：我们的数据表明，不同体型猪品种之间的IGF-1RECD单倍型影响IGF-1R表达，进而通过激活下游信号通路影响骨骼肌细胞的增殖和分化。
方法：在本研究中，将大型长白猪（LP）和小型巴马香（BM）猪的两种IGF-1RECD单倍型的编码序列克隆到pcDNA3.1载体中，以生成pcDNA3.1-LP和pcDNA3.1-BM。然后将两种重组载体转染到骨骼肌细胞中。
结果：发现IGF-1R转录本在pcDNA3.1-LP组中的表达水平高于pcDNA3.1-BM组。来自LP的IGF-1RECD促进细胞增殖和CyclinD1表达,并促进蛋白激酶B的磷酸化（产生p-AKT）。此外，来自LP的IGF-1RECD增加了细胞分化和成肌决定因子（MyoD）的表达。
结论：我们的数据表明，不同体型猪品种之间的IGF-1RECD单倍型影响IGF-1R表达，进而通过激活下游信号通路影响骨骼肌细胞的增殖和分化。
