Follistatin production by skin fibroblasts and its regulation by dexamethasone

Activin and follistatin (FS) appear to play a role in the development of th e skin and its appendages, in the inflammatory process, angiogenesis, and i n wound healing. Although there is information on the expression of activin subunits and receptors in fibroblasts and keratinocytes, there are no repo rts on the regulation of FS expression in these cells. In the present study we analyzed the splicing variants of FS mRNAs in fibroblasts from genital and nongenital skin by RT-PCR and northern analysis, and examined the induc tion of FS mRNA and protein by hormones and growth factors in skin fibrobla sts from human and nonhuman primates. FS mRNA was highly expressed in all f ibroblast strains with similar expression regardless of donor species (huma n or monkey), donor age (neonate or adult), or the organ from which the fib roblast strains were established (skin or pituitary, genital or non-genital skin). Moreover, the band density corresponding to FS-288 was < 5-10% of t he value for FS-315 in skin fibroblasts as in all other tissues examined. F ibroblast FS mRNA and protein production were biphasically regulated by dex amethasone: low concentrations (0.01 and 0.1 nM) increased whereas higher c oncentrations (> 1 nM) suppressed FS expression. On the other hand, androge ns, activin and PACAP38 were without effect. These data establish cultured skin fibroblasts as a model to study FS gene expression in humans, and supp ort a role for follistatin in the normal immune response and in the anti-in flammatory actions of glucocorticoids. (C) 2001 Elsevier Science Ireland Lt d. All rights reserved.