The Spatial and Temporal Expression Patterns of Integrin α9β1 and One of Its Ligands, the EIIIA Segment of Fibronectin, in Cutaneous Wound Healing

Abstract

The fibronectins (FN) comprise a family of adhesive extracellular matrix proteins thought to mediate important functions in cutaneous wounds. Plasma fibronectin (pFN) extravasates for days from intact hyperpermeable vessels following injury whereas mRNAs encoding the cellular fibronectins (cFN) that include two segments, termed EIIIA (EDA) and EIIIB (EDB), are expressed by wound cells. Wounds in mice null for pFN appear to heal normally whereas those in EIIIA null mice exhibit defects, suggesting that cFN may play a role when pFN is missing. Integrin alpha9beta1, a receptor for several extracellular matrix proteins as well as the EIIIA segment, is expressed normally in the basal layer of squamous epithelia. We report results from immunohistochemistry on healing wounds demonstrating that EIIIA-containing cFN are deposited abundantly but transiently from day 4 to 7 whereas EIIIB-containing cFN persist at least through day 14. Elevated expression of alpha9beta1 is seen in basal and suprabasal epidermal keratinocytes in wounds. The spatial expression patterns of cFN and alpha9beta1 are distinct, but overlap in the dermal-epidermal junction, and both are expressed contemporaneously. These observations suggest a role for alpha9beta1-EIIIA interactions in wound keratinocyte function.