Thrombospondin-1 promotes fibroblast-mediated collagen gel contraction caused by activation of latent transforming growth factor beta-1.

Abstract:

BACKGROUND:Grafting of cultured epithelium has become a useful technique for the treatment of epithelial defects, since grafted epithelial cells secrete factors promoting wound healing. We identified one such factor produced by cultured oral epithelial cells as thrombospondin-1 (TSP-1). Recently, TSP-1 was reported to act as an activator of transforming growth factor-beta1 (TGF-beta1). OBJECTIVE:The role of TSP-1 in wound healing and its mechanism were investigated in vitro and in vivo. METHODS:The cultured oral epithelial cell-conditioned medium was harvested and applied to Heparin-Sepharose affinity chromatography. Proteins were analyzed by N-Terminal sequencer. TSP-1 and the other factors were applied to fibroblasts-mediated collagen gel contraction assay. The amount of TGF-beta1 (latent TGF-beta1 (LTGF) and active TGF-beta1) in collagen gels was quantified by ELISA and Western blotting analysis. Collagen sponges were soaked with TSP-1 and implanted subcutaneously into rats. RESULTS:A 38 kDa protein secreted from cultured oral epithelial cells was found to be human TSP-1. TSP-1 promoted collagen gel contraction activity, and anti-human TSP-1 and TGF-beta1 antibody inhibited the activity. The diameters of the gels treated with LTGF and TSP-1 were reduced to a greater extent than those of gels treated with either factor alone. Although there were no significant differences in the amounts of total TGF-beta1, which include LTGF, the amount of 25 kDa TGF-beta1 was 3.30-fold greater in TSP-1-treated samples than controls. In vivo, 7 days after implantation, increased numbers of fibroblasts were observed in the sponges treated with TSP-1. CONCLUSION:These findings suggested that TSP-1 causes collagen gel contraction by activation of LTGF. TSP-1 is expected to be especially suitable for regulating wound healing.

journal_name

J Dermatol Sci

authors

Sakai K,Sumi Y,Muramatsu H,Hata K,Muramatsu T,Ueda M

doi

10.1016/s0923-1811(02)00150-0

subject

Has Abstract

pub_date

2003-04-01 00:00:00

pages

99-109

issue

2

eissn

0923-1811

issn

1873-569X

pii

S0923181102001500

journal_volume

31

pub_type

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