Endogenous thrombospondin-1 is not necessary for proliferation but is permissive for vascular smooth muscle cell responses to platelet-derived growth factor.
We have reexamined the role of endogenous thrombospondin-1 (TSP1) in growth and motility of vascular smooth muscle cells (SMCs). Based on the ability of aortic-derived SMCs isolated from TSP1 null mice and grown in the absence of exogenous TSP1 to grow at comparable rates and to a slightly higher density than equivalent cells from wild-type mice, TSP1 is not necessary for their growth. Low concentrations of exogenous TSP1 stimulate growth of TSP1 null SMCs, but higher doses of TSP1 or its C-terminal domain are inhibitory. However, SMCs from TSP1 null mice are selectively deficient in chemotactic and proliferative responses to platelet-derived growth factor and in outgrowth in three-dimensional cultures. Recombinant portions of the N- and C-terminal domains of TSP1 stimulate SMC chemotaxis through different integrin receptors. Based on these data, the relative deficiency in SMC outgrowth during an ex vivo angiogenic response of muscle tissue from TSP1 null mice is probably due to restriction of platelet-derived growth factor dependent SMC migration and/or proliferation.
Isenberg
J Scott
JS
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Building 10, Room 2A33, 10 Center Drive MSC1500 Bethesda, MD 20892-1500, United States. isenberj@mail.nih.gov
Calzada
Maria J
MJ
Zhou
Longen
L
Guo
Nenghua
N
Lawler
Jack
J
Wang
Xue-Qing
XQ
Frazier
William A
WA
Roberts
David D
DD
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007118:Immunoassay; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008168:Lung / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000737:chemistry; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D019700:Thrombospondin 1 / Q000737:chemistry / Q000502:physiology*; D013997:Time Factors
D010455:Peptides; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D019700:Thrombospondin 1; D007334:Insulin-Like Growth Factor I