title: Estrogens induce rapid cytoskeleton re-organization in human dermal fibroblasts via the non-classical receptor GPR30.
abstract: 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 non-classical 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.
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS UMR5242, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Carnesecchi
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS UMR5242, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Marilyne
authors.initials: M
authors.lastname: Malbouyres
authors.affiliation: Laboratoire interdisciplinaire de Physique UMR CNRS 5588, Université Joseph Fourier, Grenoble, France.
authors.forename: Richard
authors.initials: R
authors.lastname: de Mets
authors.affiliation: Laboratoire interdisciplinaire de Physique UMR CNRS 5588, Université Joseph Fourier, Grenoble, France.
authors.forename: Martial
authors.initials: M
authors.lastname: Balland
authors.affiliation: Laboratoires Clarins, Pontoise, France.
authors.forename: Gallic
authors.initials: G
authors.lastname: Beauchef
authors.affiliation: Laboratoires Clarins, Pontoise, France.
authors.forename: Katell
authors.initials: K
authors.lastname: Vié
authors.affiliation: PLATIM, US8 / UMS3444 BioSciences Gerland, Lyon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Chamot
authors.affiliation: PLATIM, US8 / UMS3444 BioSciences Gerland, Lyon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Lionnet
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS UMR5242, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Ruggiero
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS UMR5242, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Vanacker
mesh_terms: D000328:Adult; D052117:Benzodioxoles / Q000494:pharmacology; D020405:Dermis; D004958:Estradiol / Q000494:pharmacology*; D047629:Estrogen Receptor beta / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C568862:4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline; D052117:Benzodioxoles; D047629:Estrogen Receptor beta; D004967:Estrogens; C109584:GPER1 protein, human; D011804:Quinolines; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D004958:Estradiol; D019869:Phosphatidylinositol 3-Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3