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PDGF ligand and receptor gene expression during repair of arterial injury
M W Majesky1, M A Reidy, D F Bowen-Pope
1Department of Pathology, University of Washington, Seattle 98195.
Abstract:
Smooth muscle cells (SMC) in rat carotid artery leave the quiescent state and proliferate after balloon catheter injury, but the signals for mitogenesis are not known. In this study, the possibility that cells within damaged arteries produce a growth factor that could act locally to stimulate SMC replication and repair was examined. We found that the genes for PDGF-A and -B (ligand) and PDGF receptor (alpha and beta subunits) were expressed in normal and injured carotid arteries and were independently regulated during repair of carotid injury. Two phases of PDGF ligand and receptor gene expression were observed: (a) In the early stage, a large decrease in PDGF beta-receptor mRNA levels preceded 10- to 12-fold increases in PDGF-A transcript abundance in the first 6 h after wounding. No change in PDGF alpha-receptor or PDGF-B gene expression was found at these times. (b) In the chronic phase, 2 wk after injury, neointimal tissue had lower levels of PDGF alpha-receptor mRNA (threefold) and higher levels of PDGF beta-receptor mRNA (three- to fivefold) than did restored media. Moreover, in situ hybridization studies identified a subpopulation of neointimal SMC localized at or near the luminal surface with a different pattern of gene expression than the underlying carotid SMC. Luminal SMC were strongly positive for PDGF-A and PDGF beta-receptor transcripts, while showing little or no hybridization for PDGF-B or PDGF alpha-receptor. Immunohistochemical studies showed strongly positive staining for PDGF-A in SMC along the luminal surface. These data show that changes in PDGF ligand and receptor expression occur at specific times and locations in injured carotid artery and suggest that these changes may play a role in regulating arterial wound repair.
Insights
Platelet-derived growth factor (PDGF) gene expression changes during rat carotid artery repair after injury. These PDGF signaling changes suggest a role in regulating smooth muscle cell proliferation and arterial wound healing.
Area of Science:
- Vascular Biology
- Cell Signaling
- Molecular Medicine
Background:
- Smooth muscle cells (SMC) in rat carotid arteries proliferate after injury, but the mitogenic signals are unknown.
- Investigating local growth factor production for SMC replication and repair is crucial for understanding arterial wound healing.
Purpose of the Study:
- To examine the role of platelet-derived growth factor (PDGF) ligand and receptor gene expression in rat carotid artery repair following balloon catheter injury.
- To determine if PDGF signaling is involved in regulating smooth muscle cell proliferation during arterial wound repair.
Main Methods:
- Gene expression analysis of PDGF-A, PDGF-B, and PDGF receptors (alpha and beta subunits) in normal and injured rat carotid arteries.
- Utilizing in situ hybridization and immunohistochemistry to localize PDGF expression within neointimal SMC subpopulations.
- Comparing gene expression patterns in early (6h) and chronic (2wk) phases post-injury.
Main Results:
- PDGF-A transcript levels significantly increased within 6 hours post-injury, while PDGF beta-receptor mRNA decreased.
- In the chronic phase, neointimal SMC showed distinct PDGF expression patterns, with high PDGF-A and beta-receptor transcripts localized to the luminal surface.
- PDGF ligand and receptor gene expression were independently regulated and temporally/spatially altered during arterial repair.
Conclusions:
- Changes in PDGF ligand and receptor expression occur at specific times and locations in injured carotid arteries.
- PDGF signaling pathways are likely involved in regulating smooth muscle cell proliferation and arterial wound repair.
- Distinct SMC subpopulations at the luminal surface exhibit unique PDGF expression profiles during repair.