Hypertrophic scar (HTS) is a common pathologic dermal fibroproliferative disease after skin injury. Transforming growth factor β (TGF-β) plays a central role in HTS formation and development. Thrombospondin-1 (TSP-1) activates latent TGF-β by binding to latency-associated peptide-β on TGF-β structure. So far, LSKL peptide was shown to selectively antagonize TSP-1. In this study, TSP-1 was first confirmed to be highly expressed in HTS. LSKL peptide was proven to inhibit the overexpression of extracellular matrix and contractile ability of HTS fibroblasts. In vivo, LSKL could attenuate the thickness of HTS, distortion of collagen alignment and fibrogenesis. Results also demonstrated that LSKL peptide not only remarkably attenuated cell proliferation and migration, but also induced cell apoptosis of HTS fibroblasts. Western blot analysis further revealed that LSKL peptide significantly suppressed the phosphorylation of PI3K, AKT, and mTOR, while not affecting the phosphorylation of Smad2/3 and MEK/ERK. These findings suggested that LSKL might be a promising anti-fibrosis agent to HTS through PI3K/AKT/mTOR signaling pathway.
Keywords: Fibroblasts; Hypertrophic scar; LSKL; PI3K/AKT/mTOR; TSP-1.
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