Acceleration of Retinol-Induced Epidermal Mucous Metaplasia by Stimulating the Dermal Adenylate Cyclase-cAMP System in Chick Embryonic Skin: Appearance of cAMP-Dependent Phosphorylated Proteins in Dermis of Retinol-Pretreated Skin after 2 h-Treatment with cAMP: (retinol/epidermal mucous metaplasia/dermis/adenylate cyclase/protein phosphorylation).

Abstract

Epidermal mucous metaplasia of cultured 13-day-old chick embryonic tarsometatarsal skin can be induced by culture in medium containing excess retinol (20 μM) for only 8-24 h and then in a chemically defined medium with Bt2 cAMP (0.2-2 mM) and without retinoids or serum for 2 days. In this work, stimulation of the adenylate cyclase-cAMP system in retinol-pretreated skin by forskolin, pertussis toxin, cholera toxin or AIF4 - was found to accelerate the synthesis of epidermal sulfated glycoprotein (mucin). In skin induced toward mucous metaplasia by retinol, treatment with forskolin for 1 day increased the cAMP content 10-fold in the dermis but only 2-fold in the epidermis over the control levels. The cAMP level of Bt2 cAMP (0.2 mM)-treated skin was 18 times higher in the dermis but rather lower in the epidermis than untreated skin. These results suggest the importance of an adenylate cyclase-cAMP system in the dermis of skin in stimulating mucous metaplasia induced by retinoids. In fact, cAMP-dependent protein phosphorylation was seen only in the dermis of retinol-pretreated skin after 2 h-treatment with cAMP. As no transfer of cAMP from the dermis to the epidermis of forskolin-treated skin was detected, there may be no gap junctional communication between the epidermis and the dermis, while the basement membrane becomes discontinuous during mucous metaplasia.