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Platelet-derived gr...
Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing
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Rajkumar, Vineeth S. (författare)
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Shiwen, Xu (författare)
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- Boström, Maria (författare)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper
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Leoni, Patricia (författare)
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Muddle, John (författare)
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Ivarsson, Mikael (författare)
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- Gerdin, Bengt (författare)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper
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Denton, Christopher P. (författare)
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Bou-Gharios, George (författare)
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Black, Carol M. (författare)
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Abraham, David J. (författare)
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(creator_code:org_t)
- Elsevier BV, 2006
- 2006
- Engelska.
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 169:6, s. 2254-2265
- Relaterad länk:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.2...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Rajkumar, Vineet ...
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Shiwen, Xu
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Boström, Maria
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Leoni, Patricia
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Muddle, John
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Ivarsson, Mikael
-
visa fler...
-
Gerdin, Bengt
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Denton, Christop ...
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Bou-Gharios, Geo ...
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Black, Carol M.
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Abraham, David J ...
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visa färre...
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American Journal ...
- Av lärosätet
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Uppsala universitet