National Research Center for Sexual Medicine and Department of Urology, Inha University College of Medicine, Incheon 22332, Republic of Korea.
Department of Biomedical Sciences, College of Medicine and Program in Biomedical Science & Engineering, Inha University, Incheon 22332, Republic of Korea.
Int J Mol Sci. 2023 Feb 2;24(3):2935. doi: 10.3390/ijms24032935.
Severe vascular and nerve damage from diabetes is a leading cause of erectile dysfunction (ED) and poor response to oral phosphodiesterase 5 inhibitors. Argonaute 2 (Ago2), a catalytic engine in mammalian RNA interference, is involved in neurovascular regeneration under inflammatory conditions. In the present study, we report that Ago2 administration can effectively improve penile erection by enhancing cavernous endothelial cell angiogenesis and survival under diabetic conditions. We found that although Ago2 is highly expressed around blood vessels and nerves, it is significantly reduced in the penis tissue of diabetic mice. Exogenous administration of the Ago2 protein restored erectile function in diabetic mice by reducing reactive oxygen species production-signaling pathways (inducing eNOS Ser/NF-κB Ser signaling) and improving cavernous endothelial angiogenesis, migration, and cell survival. Our study provides new evidence that Ago2 mediation may be a promising therapeutic strategy and a new approach for diabetic ED treatment.
糖尿病引起的严重血管和神经损伤是导致勃起功能障碍（ED）和口服磷酸二酯酶 5 抑制剂反应不佳的主要原因。Argonaute 2（Ago2）是哺乳动物 RNA 干扰的催化引擎，在炎症条件下参与神经血管再生。在本研究中，我们报告了 Ago2 的给药可以通过增强海绵体内皮细胞在糖尿病条件下的血管生成和存活来有效改善阴茎勃起。我们发现，尽管 Ago2 在血管和神经周围高度表达，但在糖尿病小鼠的阴茎组织中显著减少。外源性给予 Ago2 蛋白可通过减少活性氧产生信号通路（诱导 eNOS Ser/NF-κB Ser 信号）和改善海绵体内皮细胞的血管生成、迁移和细胞存活来恢复糖尿病小鼠的勃起功能。我们的研究为 Ago2 介导可能成为一种有前途的治疗策略和治疗糖尿病 ED 的新方法提供了新的证据。
