Argonaute 2 Restores Erectile Function by Enhancing Angiogenesis and Reducing Reactive Oxygen Species Production in Streptozotocin (STZ)-Induced Type-1 Diabetic Mice

• Published in: International journal of molecular sciences Vol. 24; no. 3; p. 2935
• Main Authors: Liu, Fang-Yuan, Yin, Guo Nan, Ock, Jiyeon, Fridayana, Fitri Rahma, Niloofar, Lashkari, Huang, Yan, Vo, Minh Nhat, Suh, Jun-Kyu, Hong, Soon-Sun, Kang, Ju-Hee, Ryu, Ji-Kan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02-02-2023; MDPI
• Subjects: Ago2; Angiogenesis; Animals; Apoptosis; Argonaute 2 protein; Blood vessels; Cells; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 1 - metabolism; Endothelial cells; Erectile dysfunction; Erectile Dysfunction - drug therapy; Erectile Dysfunction - etiology; Glucose; Humans; Inflammation; Liver cancer; Male; Mammals - metabolism; Medical research; Mice; Mitochondria; Mitochondrial DNA; Nerves; NF-κB protein; Nitric Oxide Synthase Type III - metabolism; Penile Erection; Penis; Penis - blood supply; Phosphorylation; Proteins; reactive oxygen species; Reactive Oxygen Species - metabolism; Regeneration; RNA-mediated interference; Streptozocin; Streptozocin - pharmacology; Survival; diabetes; Ago2; angiogenesis; reactive oxygen species; erectile dysfunction
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.