Regulation of vascular smooth muscle cell proliferation and migration by human sprouty 2.
OBJECTIVE
To determine whether the human sprouty 2 (hSPRY2) protein, an inhibitor of receptor tyrosine kinase actions, regulates vascular smooth muscle cell (VSMC) proliferation, migration, and neointima formation in injured carotid artery.


RESULTS
The hSPRY2 protein or green fluorescent protein (GFP; control) was transduced into VSMCs by placing an N-terminal TAT epitope on the proteins. The transduction of TAT-tagged hSPRY2 (TAT-hSPRY2) but not TAT-GFP inhibited the ability of serum and different growth factors to stimulate migration of VSMCs. Likewise, TAT-hSPRY2 also inhibited VSMC proliferation in response to serum. The hSPRY2 microtubule association (amino acids 123-177) and membrane translocation (amino acids 178-194) domains were necessary for the biological actions of hSPRY2. In the rat carotid artery injury model, exposure of the injured vessel for 1 hour to TAT-hSPRY2, but not TAT-GFP, markedly inhibited growth of the neointima over the 28-day postangioplasty period as well as VSMC proliferation. The exogenously applied TAT-hSPRY2 was retained in the carotid arteries for at least 3 days after injury, and endogenous SPRY2 expression was maximized around day 14 after injury. The latter is perhaps a compensatory mechanism to regulate neointima formation.


CONCLUSIONS
We conclude that TAT-tagged proteins are efficiently transduced into VSMCs in vitro and in vivo, that hSPRY2 inhibits growth and migration of VSMCs, and that this protein can decrease neointimal growth after blood vessel injury.
Zhang
Chunxiang
C
Department of Pharmacology and Experimental Therapeutics, Loyola University, Chicago, Ill, USA.
Chaturvedi
Deepti
D
Jaggar
Laura
L
Magnuson
Debra
D
Lee
John M
JM
Patel
Tarun B
TB
D000818:Animals; D020212:Carotid Artery Injuries / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000502:physiology*; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D014161:Transduction, Genetic; D017539:Tunica Intima / Q000473:pathology / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; C485561:SPRY2 protein, human; D020794:Receptor Protein-Tyrosine Kinases