TGF-beta 1 stimulates expression of keratinocyte integrins during re-epithelialization of cutaneous wounds.
Epidermal keratinocytes migrate over a provisional matrix during the re-epithelialization of cutaneous wounds. We have investigated the expression of integrins and of transforming growth factor-beta 1 (TGF-beta 1) during re-epithelialization in a porcine model. Tissue specimens were collected at different times after injury and stained with antibodies against subunits of the fibronectin receptor, integrin alpha 5 beta 1, and the vitronectin receptor, integrin alpha v beta 5. Intense staining was observed in the migrating keratinocytes of 5-d wounds; basal and suprabasal cells were stained around the entire cell periphery. Staining returned toward normal levels in 14-d wounds. The appearance of the extracellular form of TGF-beta 1 seemed to be coordinated with the increased expression of integrin subunits: it was detected in migrating keratinocytes and in the adjacent epidermis of early wounds at 5 and 7 d. We also investigated the effect of TGF-beta 1 on cultured epidermal cells. Treating human keratinocytes with TGF-beta 1 increased the levels of mRNA for the integrin subunits alpha 5, alpha v, and beta 5, but had little effect on beta 1. The corresponding cell-surface expression of alpha 5 and alpha v was also increased after treatment. Thus, during wound repair, TGF-beta 1 may induce epidermal keratinocytes to express integrins that facilitate the migratory component of re-epithelialization.
Gailit
J
J
Department of Dermatology, School of Medicine, SUNY at Stony Brook 11794-8165.
Welch
M P
MP
Clark
R A
RA
D000818:Animals; D015152:Blotting, Northern; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000502:physiology*; D015603:Keratinocytes / Q000737:chemistry*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000293:injuries* / Q000378:metabolism; D013552:Swine; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology*; D014945:Wound Healing / Q000502:physiology*
D016023:Integrins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta