Reduced expression of PDGF and PDGF receptors during impaired wound healing.
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.
Beer
H D
HD
Max-Planck-Institut für Biochemie, Martinsried, Germany.
Longaker
M T
MT
Werner
S
S
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004817:Epidermis / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D012867:Skin / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
D005938:Glucocorticoids; D010982:Platelet-Derived Growth Factor; D003907:Dexamethasone; D017479:Receptors, Platelet-Derived Growth Factor