【摘要】 胰岛素样生长因子-1(IGF-1)基因包含6个外显子,具有转录和翻译产物多样化的特点,原因在于存在多个转录起始位点的选择性应用,转录产物的选择性剪接,以及不同多聚腺苷酸化位点的使用。长期以来人们普遍关注由外显子3和4编码的循环型IGF-1在生长发育中的作用,最近对肌肉、神经等组织自分泌/旁分泌的局部型IGF-1研究发现,选择性剪接产生的IGF-1变体具有外显子5和6编码的延伸肽(E肽),并表现出特殊的生物学功能,如IGF-1Ea、IGF-1Eb(MGF)及其E肽在骨骼肌、心肌、神经等组织中表现出促进生长和损伤修复的功能,这些特殊功能可能通过细胞表面的一种特殊E肽受体介导。更多还原

【Abstract】 The IGF-1 gene,containing six exons,is characterized by the generation of multiple heterogeneous mRNA transcripts and translations.The IGF-1 isoforms being produced arise from the combination of mutiple transcription initiation sites,alternate splicing,and different polyadenylation signals.These different mRNAs are translated to distinct circulating and local isoforms.The circulating mature IGF-1 is encoded by exons 3 and 4,and its biological function in growth and developmen has been intensively studied.The loclal isoforms of IGF-1 contains the part encoded by exons 3 and 4,and moreover the alternate extension peptide at carboxy-terminal,encoded by exons 5 and 6,is also included in the isoforms.And the functions of local IGF-1 isoforms and E-peptides have been overlooked until recently.Recently investigation shows that cell discrepant response to the overexpression of different IGF-1 isoforms and the E-peptides,and more interestingly,IGF-1Ea,IGF-1Eb(MGF) and MGF E-peptide have potential to promote skeletal muscle regeneration,to prevent cardiac muscle loss and neural damage.The acting mechanism of IGF-1 isoforms differ from the IGF-1,and the isoforms functioned probably by binding to specific E-peptide receptor,instead of binding to the IGF-1R.更多还原