Caveolin-1 expression enhances endothelial capillary tubule formation.
The level of caveolin-1 expression closely correlates with the oncogenic transformation of NIH 3T3 cells, the proliferation of human cancer cells, and the differentiation of adipocytes and muscle cells. However, the role of caveolin-1 in endothelial cell proliferation and differentiation remains unknown. Here, we have shown that angiogenic growth factors that stimulate endothelial cell proliferation lead to dramatic reductions in caveolin-1 expression. In addition, using an in vitro Matrigel assay system, we studied the potential role of caveolin-1 in capillary-like tubule formation (i.e. endothelial cell differentiation) using human microvascular endothelial cells (HMEC-1). We showed that the level of endogenous caveolin-1 expression increased in a time-dependent manner when endothelial cells underwent differentiation and that the maximum level of caveolin-1 expression occurred just prior to the formation of capillary-like tubules. Interestingly, overexpression of caveolin-1, via an adenoviral gene delivery system, clearly accelerated endothelial cell differentiation/tubule formation and led to a dramatic approximately 3-fold increase in the number of capillary-like tubular structures. Conversely, down-regulation of caveolin-1 expression, via an antisense adenoviral approach, reduced the number of capillary-like tubules formed by >10-fold. Consistent with the unique function of caveolin-1 in interacting with key signaling molecules, delivery of the caveolin-1 scaffolding domain into the cytoplasm of living endothelial cells was also sufficient to enhance capillary-like tubule formation. Taken together, these results clearly demonstrate that caveolin-1 and the caveolin-1 scaffolding domain play an important positive role in the regulation of endothelial cell differentiation, a prerequisite step in the process of angiogenesis.
Liu
Jun
J
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Wang
Xiao Bo
XB
Park
David S
DS
Lisanti
Michael P
MP
D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000166:cytology; D002196:Capillaries / Q000378:metabolism*; D002417:Cattle; D051242:Caveolin 1; D022461:Caveolins / Q000096:biosynthesis*; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D015536:Down-Regulation; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006801:Humans; D015151:Immunoblotting; D007797:Laminin / Q000494:pharmacology; D008164:Luminescent Proteins / Q000378:metabolism; D008833:Microcirculation / Q000166:cytology; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D015854:Up-Regulation
C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D004338:Drug Combinations; D007797:Laminin; D008164:Luminescent Proteins; D016376:Oligonucleotides, Antisense; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C059485:matrigel; D049452:Green Fluorescent Proteins; D003094:Collagen