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Reduced expression of PDGF and PDGF receptors during impaired wound healing
H D Beer1, M T Longaker, S Werner
1Max-Planck-Institut für Biochemie, Martinsried, Germany.
Abstract:
A series of studies has shown that application of platelet-derived growth factor (PDGF) to a wound enhances the process of wound repair, especially in animals with wound-healing defects. In the current study, we investigated the regulation of PDGF A and PDGF B and their receptors during wound repair in mice. Both ligands and both types of receptor were expressed in normal and wounded skin, whereby PDGF A and PDGF B proteins were found at different sites in the healing wound. Surprisingly, no significant induction of these genes was observed after skin injury in normal mice, and expression levels were similar at all stages of the repair process. To determine a possible role of endogenous PDGF in normal wound healing, we subsequently analyzed the regulation of PDGF and PDGF receptors during wound healing in healing-impaired animals. Genetically diabetic db/db mice showed a significant reduction in PDGF A and A-type receptor expression in nonwounded and wounded back skin. Furthermore, expression of the B-type receptor was also reduced during the repair process. Systemic glucocorticoid treatment caused a severe defect in wound repair that was accompanied by reduced expression of PDGF A and B and of the B-type receptor in the early phase of wound healing. These results provide an explanation for the beneficial effect of exogenous PDGF in the treatment of wound-healing disorders. Furthermore, our data suggest that a certain expression level of PDGF and its receptors is essential for normal repair.
Insights
Platelet-derived growth factor (PDGF) is crucial for normal wound repair. Impaired PDGF signaling in diabetic or glucocorticoid-treated mice highlights its essential role in healing processes.
Area of Science:
- Regenerative Medicine
- Molecular Biology
- Dermatology
Background:
- Platelet-derived growth factor (PDGF) application enhances wound repair, particularly in impaired healing models.
- The precise role and regulation of endogenous PDGF and its receptors during wound healing remain incompletely understood.
Purpose of the Study:
- To investigate the expression and regulation of PDGF A, PDGF B, and their receptors during normal and impaired wound repair in mice.
- To elucidate the contribution of endogenous PDGF signaling to the wound healing process.
Main Methods:
- Gene and protein expression analysis of PDGF A, PDGF B, and their receptors (PDGFRA, PDGFRB) in mouse skin.
- Comparative study in normal mice, genetically diabetic (db/db) mice, and mice treated with systemic glucocorticoids.
Main Results:
- PDGF A and B ligands and their receptors were expressed in normal and wounded skin, with distinct localization patterns.
- No significant induction of PDGF genes was observed after skin injury in normal mice.
- Diabetic mice exhibited reduced expression of PDGF A and its receptor, and also reduced B-type receptor expression.
- Glucocorticoid treatment led to severe wound repair defects and decreased expression of PDGF A, PDGF B, and the B-type receptor.
Conclusions:
- Endogenous PDGF and its receptor expression are essential for normal wound repair.
- Reduced PDGF signaling contributes to impaired wound healing in diabetic and glucocorticoid-treated conditions.
- These findings explain the therapeutic benefits of exogenous PDGF in treating wound-healing disorders.