title: Effects of estrogens on extracellular matrix synthesis in cultures of human normal and scleroderma skin fibroblasts.
abstract: To investigate the effects of 17beta-estradiol (E2) on extracellular matrix (ECM) protein synthesis (collagen type I, fibronectin, and laminin) using cultures of normal and scleroderma (SSc) skin fibroblasts. Primary fibroblasts cultures, obtained from skin biopsies of six female voluntary subjects and three female SSc patients, were treated for 24 h with E2 (10(-10)M) alone or in combination with tamoxifene (TAM, 10(-7)M) as an estrogen receptor (ER) antagonist. ECM protein synthesis was analyzed by immunocytochemistry and Western blotting. E2 induced a significant increase of fibronectin, collagen type I, and laminin synthesis both in normal (P < 0.01, P < 0.05, P < 0.01, respectively) and SSc fibroblasts (P < 0.001, P < 0.05, P < 0.001, respectively) when compared to untreated fibroblasts. TAM induced a significant decrease of ECM protein synthesis when compared to E2-treated TAM-untreated fibroblasts. This study seems to support important modulatory effects of E2 in the fibrotic progression of the SSc process via ER interactions.
authors.affiliation: Research Laboratory and Academic Unit of Clinical Rheumatology, Department Internal Medicine, University of Genova, Genova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Soldano
authors.forename: Paola
authors.initials: P
authors.lastname: Montagna
authors.forename: Renata
authors.initials: R
authors.lastname: Brizzolara
authors.forename: Alberto
authors.initials: A
authors.lastname: Sulli
authors.forename: Aurora
authors.initials: A
authors.lastname: Parodi
authors.forename: Bruno
authors.initials: B
authors.lastname: Seriolo
authors.forename: Sabrina
authors.initials: S
authors.lastname: Paolino
authors.forename: Barbara
authors.initials: B
authors.lastname: Villaggio
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
mesh_terms: D000368:Aged; D015153:Blotting, Western; D016022:Case-Control Studies; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism; D008875:Middle Aged; D012594:Scleroderma, Localized / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors
chemical_list: D024042:Collagen Type I; D004967:Estrogens; D005353:Fibronectins; D007797:Laminin; D013629:Tamoxifen; D004958:Estradiol