PECAM-1 isoform-specific regulation of kidney endothelial cell migration and capillary morphogenesis.
Platelet endothelial cell adhesion molecule-1 (PECAM-1) has been implicated in angiogenesis through its involvement in endothelial cell-cell and cell-matrix interactions and signal transduction. Recent studies indicate that the cytoplasmic domain of PECAM-1 plays an important role in its cell adhesive and signaling properties. However, the role PECAM-1 isoforms play during angiogenic events such as cell adhesion and migration requires further delineation. To gain insight into the role PECAM-1 plays during vascular development and angiogenesis, we examined the expression pattern of PECAM-1 isoforms during kidney vascularization. We show that multiple isoforms of PECAM-1 are expressed during renal vascular development with different frequencies. The PECAM-1 that lacks exons 14 and 15 (Delta14&15) was the predominant isoform detected in the renal vasculature. To further study PECAM-1 isoform-specific functions we isolated kidney endothelial cells (EC) from wild-type and PECAM-1-deficient (PECAM-1-/-) mice with B(4)-lectin-coated magnetic beads. PECAM-1-/- kidney EC showed reduced migration, inability to undergo capillary morphogenesis in Matrigel, dense peripheral focal adhesions, and peripheral cortical actin distribution compared with wild-type cells. PECAM-1-/- kidney EC secreted increased amounts of fibronectin and decreased amounts of tenascin-C and thrombospondin-1. Reexpression of Delta14&15, but not full-length, PECAM-1 in PECAM-1-/- kidney EC restored cell migration and capillary morphogenesis defects. Thus PECAM-1 may regulate the adhesive and migratory properties of kidney EC in an isoform-specific fashion through modulation of integrin activity and extracellular matrix protein expression. Our results indicate that regulated expression of specific PECAM-1 isoforms may enable EC to accommodate the different stages of angiogenesis.
Kondo
Shuji
S
Dept. of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792-4108, USA.
Scheef
Elizabeth A
EA
Sheibani
Nader
N
Sorenson
Christine M
CM
D000818:Animals; D002196:Capillaries / Q000254:growth & development*; D002448:Cell Adhesion; D002465:Cell Movement; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D007668:Kidney / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D018919:Neovascularization, Physiologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D019096:Vitronectin
D005353:Fibronectins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D020033:Protein Isoforms; D019096:Vitronectin