Pericyte-derived extracellular vesicle-mimetic nanovesicles ameliorate erectile dysfunction via lipocalin 2 in diabetic mice
SCIE
SCOPUS
- Title
- Pericyte-derived extracellular vesicle-mimetic nanovesicles ameliorate erectile dysfunction via lipocalin 2 in diabetic mice
- Authors
- GHO, YONG SONG; Limanjaya Anita1; Guo Nan Yin1; Soon-Sun Hong2; Ju-Hee Kang3; Jun-Kyu Suh1; Ji-Kan Ryu1
- Date Issued
- 2022-05
- Publisher
- Ivyspring International Publisher
- Abstract
- Diabetes mellitus is one of the main causes of erectile dysfunction (ED). Men with diabetic ED do not respond well to oral phosphodiesterase-5 inhibitors owing to neurovascular dysfunction. Pericyte-derived extracellular vesicle-mimetic nanovesicles (PC-NVs) are known to promote nerve regeneration in a mouse model of cavernous nerve injury. Here, we report that administration of PC-NVs effectively promoted penile angiogenesis and neural regeneration under diabetic conditions, thereby improving erectile function. Specifically, PC-NVs induced endothelial proliferation and migration and reduced cell apoptosis under diabetic conditions. In addition, PC-NVs induced neural regeneration in STZ-induced diabetic mice in dorsal root ganglion and major pelvic ganglion explants in vivo and ex vivo under high-glucose conditions. We found that lipocalin 2 (Lcn2) is a new target of PC-NVs in this process, demonstrating that PC-NVs exert their angiogenic and nerve-regeneration effects by activating MAP kinase and PI3K/Akt and suppressing P53 signaling pathway in an Lcn2-dependent manner. Our findings provide new conclusive evidence that PC-NVs can promote neurovascular regeneration and recovery of erectile function under diabetic conditions via an Lcn2-dependent mechanism. Thus, local administration of PC-NVs may be a promising treatment strategy for the treatment of diabetic ED. © The author(s).
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/116602
- DOI
- 10.7150/ijbs.72243
- ISSN
- 1449-2288
- Article Type
- Article
- Citation
- International Journal of Biological Sciences, vol. 18, no. 9, page. 3653 - 3667, 2022-05
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