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: Simona Ceccarelli, Sirio D'Amici, Enrica Vescarelli, Paolo Coluccio, Pietro Matricardi, Cira di Gioia, Pierluigi Benedetti Panici, Ferdinando Romano, Luigi Frati, Antonio Angeloni, Cinzia Marchese
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 18 Issue 9 Pg. 1895-907 (Sep 2014) ISSN: 1582-4934 [Electronic] England
• PMID: 25088572 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• FGF7 protein, human
• Fibroblast Growth Factor 7
• Estradiol

Topics

• Administration, Topical
• Animals
• Cell Proliferation
• Epithelium (pathology)
• Estradiol (physiology)
• Female
• Fibroblast Growth Factor 7 (administration & dosage, physiology)
• Humans
• MCF-7 Cells
• Mice
• Mucous Membrane (pathology)
• Ovariectomy
• Signal Transduction
• Vagina (pathology)
• Vaginal Diseases (drug therapy)