Expression of granulocyte colony-stimulating factor is induced in injured rat carotid arteries and mediates vascular smooth muscle cell migration.
Granulocyte colony-stimulating factor (G-CSF) is a lineage-restricted hematopoietic growth factor that stimulates proliferation and maturation of hematopoietic progenitors and is a known powerful mobilizer of bone marrow-derived stem cells. Very little has been reported on G-CSF expression and modulation of vascular smooth muscle cell (VSMC) activation. The purpose of this study was to characterize the expression and effects of G-CSF on primary human VSMC and balloon angioplasty-injured rat carotid arteries. In cultured human VSMC, G-CSF mRNA and protein expression are induced by several cytokines, with the most potent being fetal calf serum and T-lymphocyte-conditioned media. G-CSF is not expressed in naive rat carotid arteries but is induced in neointimal SMC in carotid arteries subject to balloon angioplasty. G-CSF is chemotactic for human VSMC. There is a significant difference between unstimulated cells and those treated with G-CSF at 100 and 1,000 pg/ml (P < 0.01 and 0.05 for 3 experiments). G-CSF also activates the GTPase Rac1, a regulator of cellular migration in VSMC. Inhibition of Rac1 inhibits G-CSF-driven VSMC migration. Important signal transduction protein kinases, including p44/42 MAPK, Akt, and S6 kinase, are also activated in response to G-CSF. This is the first report describing the expression of G-CSF in injured arteries and the multiple effects of G-CSF on VSMC activation. Together, our data suggest that G-CSF is an important mediator of inflammatory cell-VSMC communication and VSMC autocrine activation and may be an important mediator of the VSMC response to injury.
Chen
Xing
X
Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Kelemen
Sheri E
SE
Autieri
Michael V
MV
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D020212:Carotid Artery Injuries / Q000473:pathology* / Q000503:physiopathology*; D017536:Carotid Artery, Common / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D016179:Granulocyte Colony-Stimulating Factor; D020830:rac1 GTP-Binding Protein