title: Topical KGF treatment as a therapeutic strategy for vaginal atrophy in a model of ovariectomized mice.
abstract: One of the most frequent complaints for post-menopausal women is vaginal atrophy, because of reduction in circulating oestrogens. Treatments based on local oestrogen administration have been questioned as topic oestrogens can reach the bloodstream, thus leading to consider their safety as controversial, especially for patients with a history of breast or endometrial cancers. Recently, growth factors have been shown to interact with the oestrogen pathway, but the mechanisms still need to be fully clarified. In this study, we investigated the effect of keratinocyte growth factor (KGF), a known mitogen for epithelial cells, on human vaginal mucosa cells, and its potential crosstalk with oestrogen pathways. We also tested the in vivo efficacy of KGF local administration on vaginal atrophy in a murine model. We demonstrated that KGF is able to induce proliferation of vaginal mucosa, and we gained insight on its mechanism of action by highlighting its contribution to switch ERα signalling towards non-genomic pathway. Moreover, we demonstrated that KGF restores vaginal trophism in vivo similarly to intravaginal oestrogenic preparations, without systemic effects. Therefore, we suggest a possible alternative therapy for vaginal atrophy devoid of the risks related to oestrogen-based treatments, and a patent (no. RM2012A000404) has been applied for this study.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Ceccarelli
authors.forename: Sirio
authors.initials: S
authors.lastname: D'Amici
authors.forename: Enrica
authors.initials: E
authors.lastname: Vescarelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Coluccio
authors.forename: Pietro
authors.initials: P
authors.lastname: Matricardi
authors.forename: Cira
authors.initials: C
authors.lastname: di Gioia
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Benedetti Panici
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Romano
authors.forename: Luigi
authors.initials: L
authors.lastname: Frati
authors.forename: Antonio
authors.initials: A
authors.lastname: Angeloni
authors.forename: Cinzia
authors.initials: C
authors.lastname: Marchese
mesh_terms: D000287:Administration, Topical; D000818:Animals; D049109:Cell Proliferation; D004848:Epithelium / Q000473:pathology; D004958:Estradiol / Q000502:physiology; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000008:administration & dosage* / Q000502:physiology; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D009092:Mucous Membrane / Q000473:pathology; D010052:Ovariectomy; D015398:Signal Transduction; D014621:Vagina / Q000473:pathology; D014623:Vaginal Diseases / Q000188:drug therapy*
chemical_list: C496453:FGF7 protein, human; D051523:Fibroblast Growth Factor 7; D004958:Estradiol
keywords: keratinocyte growth factor; non-genomic ERα pathways; vaginal atrophy
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