Abstract
Hypertrophic scarring is a skin collagen disease that can occur following skin damage and is unlikely to heal or subside naturally. Since surgical treatment often worsens scarring, it is important to investigate the pathogenesis and prevention of hypertrophic scarring. Thrombospondin-1 (THBS1) is a matrix glycoprotein that can affect fibrosis by activating TGF-β1, which plays a key role in wound repair and tissue regeneration; therefore, we investigated the effects of THBS1 on the biological function of hypertrophic scar fibroblasts. THBS1 expression was measured in hypertrophic scars and adjacent tissues as well as normal fibroblasts, normal scar fibroblasts, and hypertrophic scar fibroblasts. In addition, THBS1 was overexpressed or silenced in hypertrophic scar fibroblasts to determine the effects of THBS1 on cell proliferation, apoptosis, and migration, as well as TGF-β1 expression. Finally, the role of THBS1 in hypertrophic scarring was confirmed in vivo using a mouse model. We found that THBS1 expression was increased in hypertrophic scar tissues and fibroblasts and promoted the growth and migration of hypertrophic scar fibroblasts as well as TGF-β1 expression. Interestingly, we found that si-THBS1 inhibited the occurrence and development of bleomycin-induced hypertrophic scars in vivo and downregulated TGF-β1 expression. Together, our findings suggest that THBS1 is abnormally expressed in hypertrophic scars and can induce the growth of hypertrophic scar fibroblasts by regulating TGF-β1. Consequently, THBS1 could be an ideal target for treating hypertrophic scarring.
Highlights
Hypertrophic scarring is part of the routine pathological process of wound healing but is a type of skin collagen disease that manifests as abnormal extracellular matrix (ECM) accumulation and excessive fibroblast proliferation [1]
Western blotting and real-time PCR revealed that THBS1 protein and mRNA levels were higher in hypertrophic scars than in normal tissues (Figures 1(a) and 1(b)), while immunohistochemical staining confirmed that THBS1 expression was higher in hypertrophic scars (Figure 1(c))
We found that THBS1 was significantly up-regulated in hypertrophic scar tissue
Summary
Hypertrophic scarring is part of the routine pathological process of wound healing but is a type of skin collagen disease that manifests as abnormal extracellular matrix (ECM) accumulation and excessive fibroblast proliferation [1]. Hypertrophic scarring can be caused by skin trauma, surgery, inflammation, scalds, foreign bodies, and acne [2] and involves clinical features such as redness, pruritus, and varying degrees of pain. These scars are unlikely to self-heal and do not subside naturally [3], while surgical treatment frequently leads to recurrence, further dysfunction, and a worsened appearance [4, 5]. A variety of cell growth factors are known to regulate collagen formation and catabolism; in particular, transforming growth factor-β1 (TGF-β1) has been shown to enhance the formation of hypertrophic scars [7]
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