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

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-der...

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Κύριοι συγγραφείς: Rajkumar, V, Shiwen, X, Bostrom, M, Leoni, P, Muddle, J, Ivarsson, M, Gerdin, B, Denton, C, Bou-Gharios, G, Black, C, Abraham, D
Μορφή: Journal article
Γλώσσα:English
Έκδοση: 2006
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author Rajkumar, V
Shiwen, X
Bostrom, M
Leoni, P
Muddle, J
Ivarsson, M
Gerdin, B
Denton, C
Bou-Gharios, G
Black, C
Abraham, D
author_facet Rajkumar, V
Shiwen, X
Bostrom, M
Leoni, P
Muddle, J
Ivarsson, M
Gerdin, B
Denton, C
Bou-Gharios, G
Black, C
Abraham, D
author_sort Rajkumar, V
collection OXFORD
description 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.
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spelling oxford-uuid:74801ba4-5c2d-4d8b-a06d-1f8c566cd3c92022-03-26T20:03:19ZPlatelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:74801ba4-5c2d-4d8b-a06d-1f8c566cd3c9EnglishSymplectic Elements at Oxford2006Rajkumar, VShiwen, XBostrom, MLeoni, PMuddle, JIvarsson, MGerdin, BDenton, CBou-Gharios, GBlack, CAbraham, DConnective 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.
spellingShingle Rajkumar, V
Shiwen, X
Bostrom, M
Leoni, P
Muddle, J
Ivarsson, M
Gerdin, B
Denton, C
Bou-Gharios, G
Black, C
Abraham, D
Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing.
title Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing.
title_full Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing.
title_fullStr Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing.
title_full_unstemmed Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing.
title_short Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing.
title_sort platelet derived growth factor beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing
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AT bostromm plateletderivedgrowthfactorbetareceptoractivationisessentialforfibroblastandpericyterecruitmentduringcutaneouswoundhealing
AT leonip plateletderivedgrowthfactorbetareceptoractivationisessentialforfibroblastandpericyterecruitmentduringcutaneouswoundhealing
AT muddlej plateletderivedgrowthfactorbetareceptoractivationisessentialforfibroblastandpericyterecruitmentduringcutaneouswoundhealing
AT ivarssonm plateletderivedgrowthfactorbetareceptoractivationisessentialforfibroblastandpericyterecruitmentduringcutaneouswoundhealing
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