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...
| المؤلفون الرئيسيون: | , , , , , , , , , , |
|---|---|
| التنسيق: | Journal article |
| اللغة: | English |
| منشور في: |
2006
|
| _version_ | 1826279311675490304 |
|---|---|
| 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. |
| first_indexed | 2024-03-06T23:56:49Z |
| format | Journal article |
| id | oxford-uuid:74801ba4-5c2d-4d8b-a06d-1f8c566cd3c9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:56:49Z |
| publishDate | 2006 |
| record_format | dspace |
| 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 |
| work_keys_str_mv | AT rajkumarv plateletderivedgrowthfactorbetareceptoractivationisessentialforfibroblastandpericyterecruitmentduringcutaneouswoundhealing AT shiwenx plateletderivedgrowthfactorbetareceptoractivationisessentialforfibroblastandpericyterecruitmentduringcutaneouswoundhealing AT bostromm plateletderivedgrowthfactorbetareceptoractivationisessentialforfibroblastandpericyterecruitmentduringcutaneouswoundhealing AT leonip plateletderivedgrowthfactorbetareceptoractivationisessentialforfibroblastandpericyterecruitmentduringcutaneouswoundhealing AT muddlej plateletderivedgrowthfactorbetareceptoractivationisessentialforfibroblastandpericyterecruitmentduringcutaneouswoundhealing AT ivarssonm plateletderivedgrowthfactorbetareceptoractivationisessentialforfibroblastandpericyterecruitmentduringcutaneouswoundhealing AT gerdinb plateletderivedgrowthfactorbetareceptoractivationisessentialforfibroblastandpericyterecruitmentduringcutaneouswoundhealing AT dentonc plateletderivedgrowthfactorbetareceptoractivationisessentialforfibroblastandpericyterecruitmentduringcutaneouswoundhealing AT boughariosg plateletderivedgrowthfactorbetareceptoractivationisessentialforfibroblastandpericyterecruitmentduringcutaneouswoundhealing AT blackc plateletderivedgrowthfactorbetareceptoractivationisessentialforfibroblastandpericyterecruitmentduringcutaneouswoundhealing AT abrahamd plateletderivedgrowthfactorbetareceptoractivationisessentialforfibroblastandpericyterecruitmentduringcutaneouswoundhealing |