Level of Fibronectin mRNA Is Markedly Increased in Human Chronic Wounds

Authors


  • K.C. Ongenae, MD, T.J. Phillips, MD and H.-Y. Park, PhD have indicated no significant interest with commercial supporters.

Address correspondence and reprint requests to: Hee-Young Park, PhD, Department of Dermatology, Boston University School of Medicine, 80 East Concord St., Boston, MA 02118, or e-mail: hypark@bu.edu.

Abstract

Background. Acute wound healing has been extensively investigated over the years, however, little is known about possible healing defects in chronic wounds. Fibronectin (FN) plays a critical role in different phases of wound healing and has been demonstrated to be degraded in chronic wounds by proteases. Fibroblasts cultured from chronic leg ulcers showed a higher level of FN compared to normal fibroblasts.

Objective. We explored whether the increase in FN protein in chronic wounds is due to increased FN mRNA. In addition, the level of α5β1 integrin FN cell surface receptor was also examined.

Method. Skin biopsies were taken from normal skin within a few hours of Mohs surgery and from the edge of chronic venous leg ulcers. In situ hybridization was performed to determine the level of FN mRNA. The level of integrin α5β1 was determined by immunohistochemistry.

Results. The level of FN mRNA in normal skin and acute wounds was undetectable. In contrast, FN mRNA was heavily induced throughout the dermis of chronic wounds. Immunostaining using a monoclonal antibody against the α5 subunit of integrin revealed that chronic wounds and normal skin showed undetectable levels of α5β1 integrin. A large induction of α5 was observed in acute wounds.

Conclusion. For reepithelization to occur, epidermal keratinocytes need to migrate over the wound surface, a process requiring an interaction between FN and its cell surface receptor integrin α5β1. These findings suggest that although FN mRNA is increased in chronic wounds, lack of FN cell surface receptor may prevent migration of epidermal keratinocytes in chronic wounds.

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