Abstract
Lumican is a dermatan sulfate proteoglycan highly expressed in connective tissue and has the ability to regulate collagen fibril assembly. Previous studies have shown that lumican is involved in wound healing, but the precise effects of lumican on reepithelialization and wound contraction, the two pivotal aspects of skin wound healing, have not been investigated. Here we explored the roles of lumican in fibroblast contractility, a main aspect of skin wound healing, by adopting mice skin wound healing model and the corresponding in vitro cellular experiments. Our results showed that lumican can promote skin wound healing by facilitating wound fibroblast activation and contraction but not by promoting keratinocyte proliferation and migration. Silencing of integrin α2 completely abolished the pro-contractility of lumican, indicating lumican enhances fibroblast contractility via integrin α2. Our study for the first time demonstrated that lumican can affect fibroblast’s mechanical property, which is pivotal for many important pathological processes, such as wound healing, fibrosis, and tumor development, suggesting that lumican might have a potential to be used to modulate these processes.
Highlights
Wound healing is a complex and dynamic pathological process, finely regulated by intracellular signaling and extracellular components, including cytokines, growth factors, extracellular matrix (ECM) proteins, and so on [1,2].Accumulating evidences have shown that ECM proteins play important roles in skin cells proliferation, differentiation or motility during wound healing process
After 7 days of daily topical administration, we found that recombinant glycosylated lumican protein and lumican core protein can both significantly promoted mice skin wound healing
It has been demonstrated that lumican is involved in inflammatory cells infiltration [7] and angiogenesis [24], the two substantial aspects of wound healing
Summary
Accumulating evidences have shown that ECM proteins play important roles in skin cells proliferation, differentiation or motility during wound healing process. Wound healing is delayed in sydecan-4 null mice, which is closely associated with reduced granulation tissue and wound contraction in sydecan-4 null mice compared to that in wild type littermates [4]. Dermatopontin, a tyrosine-rich ECM protein with a striking tendency to bind the small dermatan sulfate proteoglycan, can promote wound healing by affecting migration and proliferation of local cells [5]. Further investigation revealed that lumican is required for skin wound repair by showing that skin wound healing is significantly delayed in lumican null mice compared to that in wild type mice [7]. The importance of lumican in wound healing had been established, the mechanisms of how lumican affects wound healing, fibroblast behaviors, has not been studied yet
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