Involvement of transforming growth factor-alpha and its receptor in the growth response of cultured human epidermal cells to retinoic acid.
Topical application of all-trans-retinoic acid (RA) to normal or photodamaged human skin causes pronounced growth effects on the epidermis (hyperplasia) by mechanisms poorly understood. This paper describes investigations concerning the possible involvement of transforming growth factor-alpha (TGF alpha) and its receptor in the growth stimulatory response of cultured human epidermal cells to RA. In a defined medium containing epidermal growth factor (EGF), RA (0.1-1.0 microM) was found to increase epidermal cell number and size as determined by uptake of neutral red dye. The stimulatory effect of RA was inhibited by a blocking monoclonal antibody directed against the binding domain of the EGF receptor. Relative to conditioned medium from cells grown in the absence of RA, conditioned medium from epidermal cells treated with RA contained increased concentrations of functionally active TGF alpha as determined by radioimmunoassays and radioreceptor assays. In addition, we found a marked reduction in the ability of TGF alpha to bind epidermal cells treated with RA. Decreased TGF alpha binding capacity is thought to be due to the ability of RA to stimulate TGF alpha, thereby resulting in EGF receptor binding and internalization. These results lead us to speculate that RA is capable of stimulating the secretion of TGF alpha by epidermal cells in vivo. TGF alpha may then act in an autocrine manner to mediate the hyperplastic response of the epidermis to topical RA treatment.
Piazza
G A
GA
Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, OH 45239-8707.
Ritter
J L
JL
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D000078404:Epidermal Cells; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004817:Epidermis / Q000737:chemistry / Q000648:ultrastructure; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D011863:Radioimmunoassay; D016211:Transforming Growth Factor alpha / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D016211:Transforming Growth Factor alpha; D014212:Tretinoin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors