Topical KGF treatment as a therapeutic strategy for vaginal atrophy in a model of ovariectomized mice.
Topical KGF treatment as a therapeutic strategy for vaginal atrophy in a model of ovariectomized mice.
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DOI：
10.1111/jcmm.12334
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发表时间：
2014-09
影响因子：
5.3
通讯作者：
Marchese C
中科院分区：
文献类型：
--
作者：
Ceccarelli S;D'Amici S;Vescarelli E;Coluccio P;Matricardi P;di Gioia C;Benedetti Panici P;Romano F;Frati L;Angeloni A;Marchese C
绝经后妇女最常见的主诉之一是阴道萎缩，因为循环中的雌激素减少。基于局部雌激素注射的治疗一直受到质疑，因为特定的雌激素可以到达血液，从而导致认为其安全性存在争议，特别是对有乳腺癌或子宫内膜癌病史的患者。最近，生长因子已被证明与雌激素途径相互作用，但其机制仍需充分阐明。在这项研究中，我们研究了角质形成细胞生长因子(KGF)，一种已知的上皮细胞有丝分裂原，对人阴道黏膜细胞的影响，以及它与雌激素通路的潜在串扰。我们还在小鼠阴道萎缩模型上测试了KGF局部给药的体内疗效。我们证明了KGF能够诱导阴道黏膜的增殖，并通过强调其在将ERα信号转导到非基因组途径中的贡献来深入了解其作用机制。此外，我们证明了KGF在体内恢复阴道滋养功能类似于阴道内雌激素制剂，没有全身影响。因此，我们建议了一种可能的替代疗法来治疗阴道萎缩，而不存在与基于雌激素的治疗相关的风险，并申请了一项专利(NO。RM2012A000404)被应用于本研究。
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.
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DOI：
10.1097/gme.0b013e31817b6132
发表时间：
2009-01-01
影响因子：
2.7
作者：
Labrie, Fernand;Cusan, Leonello;Labrie, Claude
通讯作者：
Labrie, Claude
影响因子：
2.6
作者：
Farage, Miranda;Maibach, Howard
通讯作者：
Maibach, Howard
影响因子：
4.8
作者：
Hall, JM;McDonnell, DP
通讯作者：
McDonnell, DP
影响因子：
15.9
作者：
Chambliss, Ken L.;Wu, Qian;Shaul, Philip W.
通讯作者：
Shaul, Philip W.
DOI：
10.1165/rcmb.2006-0384oc
发表时间：
2007-07-01
影响因子：
6.4
作者：
Gomperts, Brigitte N.;Belperio, John A.;Strieter, Robert M.
通讯作者：
Strieter, Robert M.