Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing.

Rajkumar, V; Shiwen, X; Bostrom, M; Leoni, P; Muddle, J; Ivarsson, M; Gerdin, B; Denton, C; Bou-Gharios, G; Black, C; Abraham, D

Journal article

Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing.

Abstract:: Connective tissue remodeling provides mammals with a rapid mechanism to repair wounds after injury. Inappropriate activation of this reparative process leads to scarring and fibrosis. Here, we studied the effects of platelet-derived growth factor receptor-beta blockade in vivo using the platelet-derived growth factor receptor (PDGFR)-beta inhibitor imatinib mesylate on tissue repair. After 7 days, healing of wounds was delayed with significantly reduced wound closure and concomitant reduction in myofibroblast frequency, expression of fibronectin ED-A, and collagen type I. Using a collagen type I transgenic reporter mouse, we showed that inhibiting PDGFR-beta activation restricted the distribution of collagen-synthesizing cells to wound margins and dramatically reduced cell proliferation in vivo. By 14 days, treated wounds were fully closed. Blocking PDGFR-beta signaling did not prevent the differentiation of myofibroblasts in vitro but potently inhibited fibroblast proliferation and migration. In addition, PDGFR-beta inhibition in vivo was accompanied by abnormal microvascular morphogenesis reminiscent of that observed in PDGFR-beta-/- mice with significantly reduced immunostaining of the pericyte marker NG2. Imatinib treatment also inhibited pericyte proliferation and migration in vitro. This study highlights the significance of PDGFR-beta signaling for the recruitment, proliferation, and functional activities of fibro-blasts and pericytes during the early phases of wound healing.

Publication status:: Published

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APA Style

Rajkumar, V., Shiwen, X., Bostrom, M., Leoni, P., Muddle, J., Ivarsson, M., Gerdin, B., Denton, C., Bou-Gharios, G., Black, C., & Abraham, D. (2006). Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing. American Journal of Pathology, 169(6), 2254–2265.

MLA Style

Rajkumar, V., et al. “Platelet-Derived Growth Factor-Beta Receptor Activation Is Essential for Fibroblast and Pericyte Recruitment during Cutaneous Wound Healing.” American Journal of Pathology, vol. 169, no. 6, 2006, pp. 2254–65.

Chicago Style

Rajkumar, V, X Shiwen, M Bostrom, P Leoni, J Muddle, M Ivarsson, B Gerdin, et al. 2006. “Platelet-Derived Growth Factor-Beta Receptor Activation Is Essential for Fibroblast and Pericyte Recruitment during Cutaneous Wound Healing.” American Journal of Pathology 169 (6): 2254–65.
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