Counter-regulatory function of protein tyrosine phosphatase 1B in platelet-derived growth factor- or fibroblast growth factor-induced motility and proliferation of cultured smooth muscle cells and in neointima formation.
OBJECTIVE
We have previously reported that vascular injury or treatment of cultured vascular smooth muscle cells with platelet-derived growth factor-BB (PDGF-BB) or fibroblast growth factor-2 (FGF2) increases the levels of protein tyrosine phosphatase (PTP)1B. The current study was designed to test the hypothesis that PTP1B attenuates PDGF- or FGF-induced motility and proliferation of cultured cells, as well as neointima formation in injured rat carotid arteries.


RESULTS
Treatment of cultured cells with adenovirus expressing PTP1B decreased PDGF-BB- or FGF2-induced cell motility and blocked PDGF-BB- or FGF2-induced proliferation, whereas expression of dominant negative PTP1B (C215S-PTP1B) uncovered the motogenic effect of subthreshold levels of PDGF-BB or FGF2, increased neointimal and medial cell proliferation, and induced neointimal enlargement after balloon injury. The inhibitory effect of PTP1B directed against PDGF in cultured cells was associated with dephosphorylation of the PDGFbeta receptor.


CONCLUSIONS
PTP1B suppresses cell proliferation and motility in cultured smooth muscle cells treated with PDGF-BB or FGF2, and the phosphatase plays a counter-regulatory role in vascular injury-induced cell proliferation and neointima formation. Taken together with previous studies indicating increased PTP1B levels in cells treated with growth factors, the current findings are the first to report the existence of an inhibitory feedback loop involving PDGF or FGF, and PTP1B in blood vessels.
Chang
Yingzi
Y
Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, USA. ychang@physio1.utmem.edu
Ceacareanu
Bogdan
B
Zhuang
Daming
D
Zhang
Chunxiang
C
Pu
Qinghua
Q
Ceacareanu
Alice C
AC
Hassid
Aviv
A
D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects; D000077214:Becaplermin; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D025461:Feedback, Physiological / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D017539:Tunica Intima / Q000166:cytology
D000925:Anticoagulants; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516610:Ptpn1 protein, rat