Platelet-derived growth factor and transforming growth factor-beta enhance tissue repair activities by unique mechanisms.
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- G F Pierce
- Department of Pathology, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
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- T A Mustoe
- Department of Pathology, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
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- J Lingelbach
- Department of Pathology, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
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- V R Masakowski
- Department of Pathology, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
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- G L Griffin
- Department of Pathology, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
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- R M Senior
- Department of Pathology, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
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- T F Deuel
- Department of Pathology, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
抄録
<jats:p>Platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) markedly potentiate tissue repair in vivo. In the present experiments, both in vitro and in vivo responses to PDGF and TGF-beta were tested to identify mechanisms whereby these growth factors might each enhance the wound-healing response. Recombinant human PDGF B-chain homodimers (PDGF-BB) and TGF-beta 1 had identical dose-response curves in chemotactic assays with monocytes and fibroblasts as the natural proteins from platelets. Single applications of PDGF-BB (2 micrograms, 80 pmol) and TGF-beta 1 (20 micrograms, 600 pmol) were next applied to linear incisions in rats and each enhanced the strength required to disrupt the wounds at 5 d up to 212% of paired control wounds. Histological analysis of treated wounds demonstrated an in vivo chemotactic response of macrophages and fibroblasts to both PDGF-BB and to TGF-beta 1 but the response to TGF-beta 1 was significantly less than that observed with PDGF-BB. Marked increases of procollagen type I were observed by immunohistochemical staining in fibroblasts in treated wounds during the first week. The augmented breaking strength of TGF-beta 1 was not observed 2 and 3 wk after wounding. However, the positive influence of PDGF-BB on wound breaking strength persisted through the 7 wk of testing. Furthermore, PDGF-BB-treated wounds had persistently increased numbers of fibroblasts and granulation tissue through day 21, whereas the enhanced cellular influx in TGF-beta 1-treated wounds was not detectable beyond day 7. Wound macrophages and fibroblasts from PDGF-BB-treated wounds contained sharply increased levels of immunohistochemically detectable intracellular TGF-beta. Furthermore, PDGF-BB in vitro induced a marked, time-dependent stimulation of TGF-beta mRNA levels in cultured normal rat kidney fibroblasts. The results suggest that TGF-beta transiently attracts fibroblasts into the wound and may stimulate collagen synthesis directly. In contrast, PDGF is a more potent chemoattractant for wound macrophages and fibroblasts and may stimulate these cells to express endogenous growth factors, including TGF-beta, which, in turn, directly stimulate new collagen synthesis and sustained enhancement of wound healing over a more prolonged period of time.</jats:p>
収録刊行物
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- The Journal of cell biology
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The Journal of cell biology 109 (1), 429-440, 1989-07-01
Rockefeller University Press
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詳細情報 詳細情報について
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- CRID
- 1360292620677661952
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- NII論文ID
- 80004742044
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- ISSN
- 15408140
- 00219525
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