Wang Yongji, Su Xiaojing, Sorenson Christine M, Sheibani Nader
Department of Ophthalmology, University of Wisconsin, Madison, Wisconsin 53792, USA.
Am J Physiol Heart Circ Physiol. 2003 Mar;284(3):H1008-17. doi: 10.1152/ajpheart.00600.2002. Epub 2002 Nov 14.
Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a cell adhesion molecule that is highly expressed on the surface of endothelial cells and some hematopoietic cells. Its cytoplasmic domain is encoded by multiple exons, which undergo alternative splicing. Here, we demonstrate that the human PECAM-1 cytoplasmic domain undergoes alternative splicing, generating six different isoforms. RT-PCR cloning and DNA sequence analysis indicated that human tissue and endothelial cells express multiple isoforms of PECAM-1, including the full-length PECAM-1 and five other isoforms, which lack exon 12, 13, 14, or 15 or exons 14 and 15. The full-length PECAM-1 is the predominant isoform detected in human tissue and endothelial cells. This is in contrast to murine endothelium, in which the PECAM-1 isoform lacking exons 14 and 15 is the predominant isoform. The PECAM-1 isoform lacking exon 13 detected in human tissue and endothelial cells is absent in murine endothelium. The expression pattern of PECAM-1 isoforms changes during tube formation of endothelial cells on Matrigel, which may indicate specialized roles for specific isoforms of PECAM-1 during angiogenesis. The data presented here demonstrate that human PECAM-1 undergoes alternative splicing, generating multiple isoforms in vascular beds of various tissues. Therefore, the regulated expression of these isoforms may influence endothelial cell adhesive properties during angiogenesis and/or vasculogenesis.
血小板内皮细胞黏附分子-1（PECAM-1）是一种细胞黏附分子，在内皮细胞和一些造血细胞表面高度表达。其胞质结构域由多个外显子编码，这些外显子会发生可变剪接。在此，我们证明人PECAM-1胞质结构域会发生可变剪接，产生六种不同的异构体。逆转录-聚合酶链反应（RT-PCR）克隆和DNA序列分析表明，人体组织和内皮细胞表达多种PECAM-1异构体，包括全长PECAM-1和其他五种异构体，它们缺少外显子12、13、14或15，或者缺少外显子14和15。全长PECAM-1是在人体组织和内皮细胞中检测到的主要异构体。这与小鼠内皮不同，在小鼠内皮中，缺少外显子14和15的PECAM-1异构体是主要异构体。在人体组织和内皮细胞中检测到的缺少外显子13的PECAM-1异构体在小鼠内皮中不存在。PECAM-1异构体的表达模式在内皮细胞在基质胶上形成管腔的过程中发生变化，这可能表明PECAM-1的特定异构体在血管生成过程中具有特殊作用。此处呈现的数据表明人PECAM-1会发生可变剪接，在各种组织的血管床中产生多种异构体。因此，这些异构体的调控表达可能会在血管生成和/或血管发生过程中影响内皮细胞的黏附特性。
