Expression pattern of alternatively spliced PECAM-1 isoforms inretinal vasculature

[摘要] Purpose: Platelet/endothelial cell adhesion molecule-1 (PECAM-1) isa cell adhesion-signaling molecule with important roles in angiogenesisand inflammation. The alternative splicing of the PECAM-1 cytoplasmicdomain modulates its adhesive properties during vascular development andangiogenesis. This study was designed to identify alternatively splicedPECAM-1 isoforms in human and murine retina and during postnatalvascularization of murine retina.Methods: RT-PCR, DNA sequencing, and Western blot analysis wereutilized to examine the expression pattern of alternatively splicedPECAM-1 isoforms in human and mouse retina, and during vascularizationof murine retina.Results: We demonstrate that the PECAM-1 cytoplasmic domainundergoes alternative splicing generating multiple isoforms in vascularbeds of human and mouse retina. We detected full length PECAM-1 and anisoform that lacks exon 14 (Δ14) in human retina. Seven isoformsof PECAM-1 were detected in murine retina. These included full length,Δ12, Δ14, Δ15, Δ12&15, Δ14&15, andΔ12, 14&15 PECAM-1 isoforms. The full length PECAM-1 was thepredominant isoform detected in human retina, while the isoform lackingexon 14&15 (Δ14&15) was the predominant isoform detectedin murine retina. In addition, the expression pattern of PECAM-1isoforms changed during vascularization of murine retina.Conclusions: PECAM-1 mRNA undergoes alternative splicing generatingmultiple isoforms in human and murine retinal vasculature. The regulatedexpression pattern of these isoforms may influence endothelial celladhesive properties impacting vasculogenesis and angiogenesis.

[学科分类] 生物化学/生物物理