Department of Endocrinology, China-Japan Union Hospital of Jilin University, Changchun, China.
Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, China.
J Cell Mol Med. 2019 May;23(5):3257-3270. doi: 10.1111/jcmm.14212. Epub 2019 Feb 7.
As a major class of regulatory genes in majority metazoans, microRNAs (miRs) play an important role in various diseases including diabetes mellitus (DM). Lack of androgens has previously been associated with DM-induced erectile dysfunction (DMED). In addition, the biological functioning of androgen is mediated by androgen receptor (AR). Herein, we sought to investigate whether miRs participate in AR-associated DMED. Sprague-Dawlay rats were employed to establish DMED models. After modelling, levels of miR-205 and AR in their cavernous bodies were measured. The relationship between miR-205 and AR was verified using a dual-luciferase reporter gene assay. The underlying regulatory mechanisms of miR-205 were investigated in concert with the treatment of mimics or inhibitors of miR-205, or AR overexpression in the cavernous smooth muscle cells (CSMCs) isolated from rats with DMED. Meanwhile, the effects of miR-205 and AR on cell proliferation and apoptosis were evaluated using MTT assay and flow cytometry respectively. Rats with DMED presented with increased miR-205 and decreased AR levels in the cavernous bodies. AR was identified as a target gene of miR-205. Down-regulation of miR-205 or up-regulation of AR could increase proliferation and inhibits apoptosis of CSMCs in addition to improvements in the erectile functioning of rats with DMED. In summary, miR-205 may contribute to the pathogenesis of DMED via down-regulation of AR expressions.
作为大多数后生动物中主要的调控基因家族,microRNAs(miRs)在包括糖尿病(DM)在内的各种疾病中发挥着重要作用。雄激素缺乏与 DM 引起的勃起功能障碍(DMED)有关。此外,雄激素的生物学功能是由雄激素受体(AR)介导的。本研究旨在探讨 miR 是否参与 AR 相关的 DMED。采用 Sprague-Dawlay 大鼠建立 DMED 模型。建模后,测量其海绵体中的 miR-205 和 AR 水平。使用双荧光素酶报告基因检测验证 miR-205 和 AR 之间的关系。通过在 DMED 大鼠分离的海绵平滑肌细胞(CSMCs)中用 miR-205 模拟物或抑制剂或 AR 过表达处理,研究 miR-205 的潜在调控机制。同时,通过 MTT 检测和流式细胞术分别评估 miR-205 和 AR 对细胞增殖和凋亡的影响。DMED 大鼠的海绵体中 miR-205 水平升高,AR 水平降低。AR 被鉴定为 miR-205 的靶基因。下调 miR-205 或上调 AR 可增加 CSMCs 的增殖并抑制其凋亡,同时改善 DMED 大鼠的勃起功能。总之,miR-205 可能通过下调 AR 表达而导致 DMED 的发病机制。