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Quintessence Publishing: Journals: OBM


Oral Biosciences & Medicine

Edited by Birgitte Nauntofte, Jesper Reibel. Peter A. Reichart, Jim Sciubba, and Joanna M. Zakrzewska

Official publication of the European Society for Oral Laser Applications

ISSN 1742-3287

Oral Biosciences & Medicine

Year 2005
Volume 2 , Issue 2

Pages: 153 - 161

Activation of Latent TGF-1 by Thromobospondin-1 is a Major Component of Wound Repair

Nor, Jacques E./DiPietro, Luisa/Murphy-Ullrich, Joanne E./Hynes, Richard O./Lawler, Jack/Polverini, Peter J.

Purpose: Thrombospondin 1 (TSP1) is a matrix glycoprotein that regulates cell adhesion, migration, and proliferation, and is a natural inhibitor of angiogenesis. Recent evidence suggests that TSP1 is a major physiologic activator of latent transforming growth factor-β1 (TGF-β1), and that TGF-β1 is important for wound healing. The purpose of this study was to examine whether excisional wound healing in TSP1-deficient mice is compromised as a result of deficient TGF-β1 activation.
Materials and Methods: Punch wounds were made on the dorsum of TSP1 deficient and wild-type mice and the area of granulation tissue, number of microvessels, and inflammatory cell infiltration was evaluated over a period of 28 days.
Results: TSP1 deficient mice showed impaired wound healing with persistent granulation tissue, decreased collagen content over time, and delayed arrival of macrophages compared to wild-type littermates. The number of microvessels in wounds of TSP1-deficient mice was approximately two-fold greater than in wild-type littermates 10 days after injury. Topical application of TSP1, or KRFK (a peptide derived from TSP1 that activates latent TGF-β1), to wounds of TSP1-deficient mice rescued wildtype patterns of wound repair and partially recovered local levels of TGF-β1 expression. Topical application of anti-TGF-β neutralizing antibody impaired the ability of KRFK to rescue normal patterns of wound neovascularization in TSP1-deficient mice.
Conclusions: These results demonstrate that TSP1 plays a key role in the orchestration of wound healing, and that TSP1-mediated activation of local TGF-β1 is an important step in this process.

Keywords: angiogenesis, neovascularization, oral cavity, apoptosis


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