Heparan Sulfate Reduction to Enhance Wound Induced Neogenesis

Abstract

Heparan sulfate regulates cell signaling important in wound healing and regeneration. In normal mammalian wound healing, injuries that penetrate the dermis result in a scar lacking hair follicles and subcutaneous fat because hair and fat do not regenerate. However, if the dermal wound is larger than a critical size (≥20 mm in adult mice) a process termed ‘Wound Induced Neogenesis’ occurs and some neogenic hair and fat is regenerated in the center of the wound. Based on previous observation that a deficiency in heparan sulfate accelerates cutaneous wound healing in mice, we hypothesized that heparan sulfate deficiency can enhance wound induced neogenesis of hair and fat in dermal wounds. Using systemic genetic models of heparan sulfate deficiency (Ext1+/−Ext2+/−), we tested whether mice with less heparan sulfate had enhanced wound induced neogenesis of hair and fat after a subcritical size (15 mm) full‐thickness dorsal skin excisional wound. Although we observed no significant difference in the rate or extent of wound closure, we found increased neogenesis of hair follicles and fat in heparan sulfate deficient mice. Our experiments suggest that inducing heparan sulfate deficiency can be a therapeutic avenue to enhance mammalian regeneration.Support or Funding InformationThis work was supported by the National Institute of Arthritis, Muscular, and Skin Diseases (R61 AR073031).