Inhibitory effect of TGF-β peptide antagonist on the fibrotic phenotype of human hypertrophic scar fibroblasts.

CONTEXT: TGF-β plays a central role in hypertrophic scar (HS) formation and development.

OBJECTIVE

This study investigated the role of a TGF-β antagonist peptide in inhibiting fibrotic behavior of human HS-derived fibroblasts (HSFs).

MATERIALS AND

METHODS

HSFs were seeded at a density of 3.1 × 10(4)/cm(2) and were subjected to treatment of peptide antagonist (30 μM) or TGF-β receptor inhibitor LY2109761 (10 μM) or without treatment followed by the analyses of quantitative PCR, Elisa, in vitro wounding and fibroblast-populated collagen lattice (FPCL) assays.

RESULTS

qPCR and Elisa analyses showed that the peptide could, respectively, reduce the gene (at 48 h) and protein (at 72 h) expression levels of collagen I (86 ± 4.8%; 56.6 ± 7.3%), collagen III (73 ± 10.7%; 43.7 ± 7.2%), fibronectin (90 ± 8.9%; 21.1 ± 2.8%), and TGF-β1 (85 ± 9.3%; 25.0 ± 9.4%) as opposed to the non-treated group (p < 0.05), as the LY2109761 group similarly did. Cell proliferation was also significantly inhibited at day 5 (CCK-8 assay) by both peptide and LY2109761 treatments compared with the non-treated group (p < 0.05). The peptide also significantly inhibited cell migration as opposed to blank control at 24 h (43 ± 6.7% versus 60 ± 2.1%, p < 0.05) and at 48 h (63.9 ± 3.1% versus 95 ± 4.1%, p < 0.05). Similar to LY2109761, the peptide antagonist significantly reduced HS FPCL contraction compared with the non-treated group with significant differences in surface area at 48 h (0.71 ± 0.06 cm(2) versus 0.51 ± 0.06 cm(2), p < 0.05) and at 72 h (0.65 ± 0.02 cm(2) versus 0.42 ± 0.01 cm(2), p < 0.05).

CONCLUSION

The TGF-β antagonist peptide may serve as an important drug for HS prevention and reduction given the obvious benefits of good biosafety, low cost, and easy manufacture and delivery.