MicroRNA‐205 is associated with diabetes mellitus‐induced erectile dysfunction via down‐regulating the androgen receptor

Abstract

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.

miR-205 Expression Elevated With EDS Treatment and Induced Leydig Cell Apoptosis by Targeting RAP2B via the PI3K/AKT Signaling Pathway

“…Exogenous overexpression of miR-205 in mouse granulosa cells promoted apoptosis and increased caspase-3/9 activity. The expression of miR-205 was increased in rat cavernous smooth muscle cells, which inhibited cell proliferation and promoted apoptosis by targeting AR (Wen et al, 2019). Taking those studies and ours together, miR-205 plays a role in promoting apoptosis.…”

Epigenetic silencing of microRNA‐874‐3p implicates in erectile dysfunction in diabetic rats by activating the Nupr1/Chop‐mediated pathway

“…15 Another study showed that miR-205 is associated with the progression of DMED. 16 In addition, decreased expression of miR-141 is associated with up-regulation of the RhoA/ROCK pathway in DMED rats. 17 These studies together demonstrate that miR-NAs may be up-or downregulated in DMED, therefore modulating the severity of DMED.…”

Couplet medicines of leech and centipede granules improve erectile dysfunction via inactivation of the CaSR/PLC/PKC signaling in streptozotocin-induced diabetic rats

“…Erectile dysfunction (ED) is characterized by the distinctive inability to achieve or maintain a sufficient erectile function for satisfaction during sexual activity [1], which was also accompanied by hypertension, coronary atherosclerosis, and diabetes mellitus [2]. ED is also known as impotency in men, estimated on 322 million men would suffer from ED global by the year 2025 [3], threatening human health, spousal relationship, and family life.…”