Exogenous administration of heparin-binding epidermal growth factor-like growth factor improves erectile function in mice with bilateral cavernous nerve injury.

Minh Nhat VO; Mi-Hye KWON; Fang-Yuan LIU; Fitri Rahma FRIDAYANA; Yan HUANG; Soon-Sun HONG; Ju-Hee KANG; Guo Nan YIN; Ji-Kan RYU

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Exogenous administration of heparin-binding epidermal growth factor-like growth factor improves erectile function in mice with bilateral cavernous nerve injury.

Author: Minh Nhat VO ¹ ; Mi-Hye KWON ¹ ; Fang-Yuan LIU ¹ ; Fitri Rahma FRIDAYANA ¹ ; Yan HUANG ¹ ; Soon-Sun HONG ² ; Ju-Hee KANG ³ ; Guo Nan YIN ¹ ; Ji-Kan RYU ¹
Author Information

1. National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon 22332, Korea.
2. Department of Biomedical Sciences, College of Medicine, Program in Biomedical Science and Engineering, Inha University, Incheon 22332, Korea.
3. Department of Pharmacology, Medicinal Toxicology Research Center, Inha University College of Medicine, Incheon 22212, Korea.
Publication Type:Journal Article
Keywords: HB-EGF; cavernous nerve injury; erectile dysfunction; nerve regeneration; reactive oxygen species
MeSH: Animals; Male; Heparin-binding EGF-like Growth Factor/therapeutic use*; Erectile Dysfunction/etiology*; Mice; Penis/drug effects*; Nerve Regeneration/drug effects*; Penile Erection/drug effects*; Peripheral Nerve Injuries/drug therapy*; Cell Proliferation/drug effects*; Apoptosis/drug effects*; Cell Movement/drug effects*; Prostatectomy/adverse effects*; Mice, Inbred C57BL; Reactive Oxygen Species/metabolism*
From: Asian Journal of Andrology 2025;27(6):697-706
CountryChina
Language:English
Abstract: Prostate cancer is the second most common malignancy and the sixth leading cause of cancer-related death in men worldwide. Radical prostatectomy (RP) is the standard treatment for localized prostate cancer, but the procedure often results in postoperative erectile dysfunction (ED). The poor efficacy of phosphodiesterase 5 inhibitors after surgery highlights the need to develop new therapies to enhance cavernous nerve regeneration and improve the erectile function of these patients. In the present study, we aimed to examine the potential of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in preserving erectile function in cavernous nerve injury (CNI) mice. We found that HB-EGF expression was reduced significantly on the 1 st day after CNI in penile tissue. Ex vivo and in vitro studies showed that HB-EGF promotes major pelvic ganglion neurite sprouting and neuro-2a (N2a) cell migration. In vivo studies showed that exogenous HB-EGF treatment significantly restored the erectile function of CNI mice to 86.9% of sham levels. Immunofluorescence staining showed that mural and neuronal cells were preserved by inducing cell proliferation and reducing apoptosis and reactive oxygen species production. Western blot analysis showed that HB-EGF upregulated protein kinase B and extracellular signal-regulated kinase activation and neurotrophic factor expression. Overall, HB-EGF is a major promising therapeutic agent for treating ED in postoperative RP.