Estrogens Induce Rapid Cytoskeleton Re-Organization in Human Dermal Fibroblasts via the Non-Classical Receptor GPR30
Résumé
The post-menopausal decrease in estrogen circulating levels results in rapid skin deterioration pointing out to a protective effect exerted by these hormones. The identity of the skin
cell type responding to estrogens is unclear as are the cellular and molecular processes
they elicit. Here, we reported that lack of estrogens induces rapid re-organization of the
human dermal fibroblast cytoskeleton resulting in striking cell shape change. This morphological change was accompanied by a spatial re-organization of focal adhesion and a substantial reduction of their number as evidenced by vinculin and actin co-staining. Cell
morphology and cytoskeleton organization was fully restored upon 17β-estradiol (E2) addition. Treatment with specific ER antagonists and cycloheximide respectively showed that
the E2 acts independently of the classical Estrogen Receptors and that cell shape change
is mediated by non-genomic mechanisms. E2 treatment resulted in a rapid and transient
activation of ERK1/2 but not Src or PI3K. We show that human fibroblasts express the nonclassical E2 receptor GPR30 and that its agonist G-1 phenocopies the effect of E2. Inhibiting GPR30 through treatment with the G-15 antagonist or specific shRNA impaired E2
effects. Altogether, our data reveal a novel mechanism by which estrogens act on skin fibroblast by regulating cell shape through the non-classical G protein-coupled receptor GPR30
and ERK1/2 activation.
Domaines
Biophysique [physics.bio-ph]
Origine : Fichiers éditeurs autorisés sur une archive ouverte