title: Dynamic Regulation of Integrin α6β4During Angiogenesis: Potential Implications for Pathogenic Wound Healing.
abstract: OBJECTIVE
  Angiogenesis is an essential component of normal cutaneous wound repair, but is altered in pathogenic forms of wound healing, such as chronic wounds and fibrosis. We previously reported that endothelial expression of integrin α6β4is developmentally regulated, with α6β4expression correlating with tissue maturation and further showed that endothelial α6β4is downregulated in explant angiogenesis assays. These data support the hypothesis that dynamic regulation of α6β4may play an important role during new vessel formation in healing wounds.
  
  
  METHODS
  To test this hypothesis, we examined the endothelial expression of α6β4using a murine model of cutaneous wound healing andin vitrocultures of primary human dermal microvascular endothelial cells (HDMECs).
  
  
  RESULTS
  Expression of α6β4is downregulated during early stages of wound healing; angiogenic vessels in day 7 wounds do not express α6β4. Endothelial expression of α6β4is resumed in day 14 wounds. Moreover, explanted HDMECs do not express α6β4, but expression is induced by treatment with histone deacetylase inhibitors.
  
  
  METHODS
  We providein vivodata supporting a role for the dynamic regulation of α6β4during vessel formation and remodeling during cutaneous wound repair andin vitrofindings that suggest endothelial β4expression is regulated transcriptionally, providing an important foundation for future studies to understand the transcriptional mechanisms involved in endothelial cell maturation during normal wound repair.
  
  
  CONCLUSIONS
  Our data indicate that α6β4is dynamically regulated during angiogenesis and vessel maturation and suggest that disruption of this regulation may contribute to defective angiogenesis associated with diabetic wounds or cutaneous fibrosis.
authors: Department of Pathology, University of Utah Hospital , Salt Lake City, Utah.
authors: Diana
authors: D
authors: Desai
authors: Department of Molecular Biology, Princeton University , Princeton, New Jersey.
authors: Purva
authors: P
authors: Singh
authors: Center for Cell Biology and Cancer Research, Albany Medical College , Albany, New York.
authors: Livingston
authors: L
authors: Van De Water
authors: Center for Cell Biology and Cancer Research, Albany Medical College , Albany, New York.
authors: Susan E
authors: SE
authors: Laflamme