AIF-1 expression modulates proliferation of human vascular smooth muscle cells by autocrine expression of G-CSF.
OBJECTIVE
Allograft inflammatory factor-1 (AIF-1) is associated with vascular smooth muscle cell (VSMC) activation and vascular injury. The purpose of this study was to characterize the molecular mechanism of AIF-1 growth-enhancing effects in human VSMC.


RESULTS
Primary human VSMCs were stably transduced with AIF-1 retrovirus (RV). Impact on cell growth was evaluated by the increase in cell number, and the effects on gene expression were determined by cDNA microarray analysis. AIF-RV overexpressing cells grew significantly more rapidly than empty-RV control cells in growth medium and serum-reduced medium (P<0.01 and 0.02, respectively). cDNA microarray analysis and Western blotting on serum-starved AIF-1-transduced VSMCs identified increased mRNA expression of several cell cycle proteins and, surprisingly, the cytokine G-CSF. Addition of G-CSF caused a 75% increase in proliferation of VSMCs in the absence of serum growth factors. The proliferative effects of AIF-1 were abrogated by neutralizing antibodies to G-CSF (P<0.05), and AIF-1-transduced VSMCs are chemotactic for human monocytes. Increased expression of G-CSF and colocalization with AIF-1 positive cells were seen in diseased, not normal human coronary arteries.


CONCLUSIONS
This study indicates that AIF-1 enhances VSMC growth by autocrine production of G-CSF, and AIF-1 expression may influence VSMC-inflammatory cell communication.
Chen
Xing
X
Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Penn 19140, USA.
Kelemen
Sheri E
SE
Autieri
Michael V
MV
D019898:Autocrine Communication / Q000502:physiology*; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology / Q000293:injuries / Q000473:pathology; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D008840:Microfilament Proteins; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014161:Transduction, Genetic; D017539:Tunica Intima / Q000473:pathology
C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D011993:Recombinant Fusion Proteins; D016179:Granulocyte Colony-Stimulating Factor