Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210004, China.
Department of Obstetrics and Gynecology, The Second Hospital of Anhui Medical University, Anhui, 230601, China.
Sci Rep. 2019 Oct 8;9(1):14456. doi: 10.1038/s41598-019-50902-w.
Vaginitis is very common among women, especially women of childbearing age, and is associated with significantly increased risk of preterm birth and pelvic inflammatory diseases. An imbalance in the vaginal flora, the primary cause of vaginitis, promotes the initiation and progression of vaginal infections. However, the responsible mechanisms are still poorly understood. Using a murine vaginitis model of Escherichia coli infection, we demonstrated that decreased expression of microRNA1976 and increased expression of CD105 and integrin αvβ6 were closely associated with the progression of vaginal infection. Importantly, we demonstrated for the first time that the microRNA1976/CD105/integrin αvβ6 axis regulates E. coli-mediated vaginal infection in mice, as evidenced by the finding that E. coli-induced vaginal infection was reversed by microRNA1976 overexpression and exacerbated by CD105 overexpression. The regulation of CD105 and integrin αvβ6 by microRNA1976 was further confirmed in a murine model of vaginitis with adenoviral vector treatment. Taken together, our data suggested that microRNA1976 negatively regulates E. coli-induced vaginal infection in mice at least in part by suppressing CD105 and integrin αvβ6 expression. These findings may provide new insight into the mechanisms of E. coli-induced vaginitis, identify a novel diagnostic biomarker and a potential therapeutic target for flora imbalance-associated vaginitis.
阴道炎在女性中非常常见，尤其是育龄妇女，与早产和盆腔炎的风险显著增加有关。阴道菌群失衡是阴道炎的主要原因，它促进了阴道感染的发生和发展。然而，其相关的作用机制仍知之甚少。我们使用大肠杆菌感染的小鼠阴道炎模型证明，miR-1976 的表达降低和 CD105 和整合素 αvβ6 的表达增加与阴道感染的进展密切相关。重要的是，我们首次证明了 microRNA1976/CD105/整合素 αvβ6 轴调节大肠杆菌介导的小鼠阴道感染，因为发现 microRNA1976 的过表达逆转了大肠杆菌诱导的阴道感染，而 CD105 的过表达则加剧了这种感染。腺病毒载体治疗小鼠阴道炎模型进一步证实了 microRNA1976 对 CD105 和整合素 αvβ6 的调节作用。综上所述，我们的数据表明，microRNA1976 通过抑制 CD105 和整合素 αvβ6 的表达，至少部分地负调控大肠杆菌诱导的小鼠阴道感染。这些发现可能为大肠杆菌诱导的阴道炎的发病机制提供新的见解，确定与菌群失衡相关的阴道炎的新的诊断生物标志物和潜在治疗靶点。
