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Int J Biol Sci 2023; 19(9):2663-2677. doi:10.7150/ijbs.81809 This issue Cite

Research Paper

Heme-binding protein 1 delivered via pericyte-derived extracellular vesicles improves neurovascular regeneration in a mouse model of cavernous nerve injury

Jiyeon Ock1,*, Jitao Wu2,*, Fang-Yuan Liu1, Fitri Rahma Fridayana1, Lashkari Niloofar1, Minh Nhat Vo1, Soon-Sun Hong3, Ju-Hee Kang4, Jun-Kyu Suh1, Guo Nan Yin1,✉, Hai-Rong Jin2,✉, Ji-Kan Ryu1,✉

1. National Research Center for Sexual Medicine and Department of Urology, Inha University College of Medicine, Incheon, 22332, Republic of Korea.
2. Department of Urology, Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University, Yantai, Shandong 264000, People's Republic of China.
3. Department of Biomedical Sciences, College of Medicine, Program in Biomedical Science & Engineering, Inha University, Incheon, Korea.
4. Department of Pharmacology, Medicinal Toxicology Research Center, Inha University College of Medicine, Incheon, Korea.
*These authors contributed equally to this work.

✉ Corresponding authors: Ji-Kan Ryu, MD, PhD, National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, 7-206, 3rd ST, Shinheung-Dong, Jung-Gu, Incheon 400-711, Republic of Korea. Tel: 82-32-890-3439; More

Citation:
Ock J, Wu J, Liu FY, Fridayana FR, Niloofar L, Vo MN, Hong SS, Kang JH, Suh JK, Yin GN, Jin HR, Ryu JK. Heme-binding protein 1 delivered via pericyte-derived extracellular vesicles improves neurovascular regeneration in a mouse model of cavernous nerve injury. Int J Biol Sci 2023; 19(9):2663-2677. doi:10.7150/ijbs.81809. https://www.ijbs.com/v19p2663.htm
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Abstract

Graphic abstract

As a peripheral nerve injury disease, cavernous nerve injury (CNI) caused by prostate cancer surgery and other pelvic surgery causes organic damage to cavernous blood vessels and nerves, thereby significantly attenuating the response to phosphodiesterase-5 inhibitors. Here, we investigated the role of heme-binding protein 1 (Hebp1) in erectile function using a mouse model of bilateral CNI, which is known to promote angiogenesis and improve erection in diabetic mice. We found a potent neurovascular regenerative effect of Hebp1 in CNI mice, demonstrating that exogenously delivered Hebp1 improved erectile function by promoting the survival of cavernous endothelial-mural cells and neurons. We further found that endogenous Hebp1 delivered by mouse cavernous pericyte (MCP)-derived extracellular vesicles promoted neurovascular regeneration in CNI mice. Moreover, Hebp1 achieved these effects by reducing vascular permeability through regulation of claudin family proteins. Our findings provide new insights into Hebp1 as a neurovascular regeneration factor and demonstrate its potential therapeutic application to various peripheral nerve injuries.

Keywords: Cavernous nerve injury, Peripheral nerve injury, Heme-binding protein 1, Extracellular vesicles, Neurovascular regeneration

Citation styles

APA
Ock, J., Wu, J., Liu, F.Y., Fridayana, F.R., Niloofar, L., Vo, M.N., Hong, S.S., Kang, J.H., Suh, J.K., Yin, G.N., Jin, H.R., Ryu, J.K. (2023). Heme-binding protein 1 delivered via pericyte-derived extracellular vesicles improves neurovascular regeneration in a mouse model of cavernous nerve injury. International Journal of Biological Sciences, 19(9), 2663-2677. https://doi.org/10.7150/ijbs.81809.

ACS
Ock, J.; Wu, J.; Liu, F.Y.; Fridayana, F.R.; Niloofar, L.; Vo, M.N.; Hong, S.S.; Kang, J.H.; Suh, J.K.; Yin, G.N.; Jin, H.R.; Ryu, J.K. Heme-binding protein 1 delivered via pericyte-derived extracellular vesicles improves neurovascular regeneration in a mouse model of cavernous nerve injury. Int. J. Biol. Sci. 2023, 19 (9), 2663-2677. DOI: 10.7150/ijbs.81809.

NLM
Ock J, Wu J, Liu FY, Fridayana FR, Niloofar L, Vo MN, Hong SS, Kang JH, Suh JK, Yin GN, Jin HR, Ryu JK. Heme-binding protein 1 delivered via pericyte-derived extracellular vesicles improves neurovascular regeneration in a mouse model of cavernous nerve injury. Int J Biol Sci 2023; 19(9):2663-2677. doi:10.7150/ijbs.81809. https://www.ijbs.com/v19p2663.htm

CSE
Ock J, Wu J, Liu FY, Fridayana FR, Niloofar L, Vo MN, Hong SS, Kang JH, Suh JK, Yin GN, Jin HR, Ryu JK. 2023. Heme-binding protein 1 delivered via pericyte-derived extracellular vesicles improves neurovascular regeneration in a mouse model of cavernous nerve injury. Int J Biol Sci. 19(9):2663-2677.

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