{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:08:12Z","timestamp":1788343692063,"version":"build-2803163510"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"Korean government","award":["NRF-2015R1C1A1A02036820"],"award-info":[{"award-number":["NRF-2015R1C1A1A02036820"]}]},{"DOI":"10.13039\/100013227","name":"Korean Health Technology R&D Project, Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["H15C0508"],"award-info":[{"award-number":["H15C0508"]}],"id":[{"id":"10.13039\/100013227","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jsm.jsexmed.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Diabetic erectile dysfunction is a disease mostly of vascular origin and men with diabetic erectile dysfunction respond poorly to oral phosphodiesterase-5 inhibitors. Hepatocyte growth factor (HGF) is a pleiotropic factor that plays an essential role in the regulation of cell proliferation, survival, and angiogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To determine the effectiveness of recombinant human (rh)-HGF in restoring erectile function in diabetic mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four groups of mice were used: control non-diabetic mice and streptozotocin-induced diabetic mice receiving two successive intracavernous injections of phosphate buffered saline (days \u22123 and 0), a single intracavernous injection of rh-HGF (day 0), or two successive intracavernous injections of rh-HGF (days \u22123 and 0). We also examined the effect of rh-HGF in primary cultured mouse cavernous endothelial cells and in major pelvic ganglion culture in vitro, which was incubated under a normal-glucose (5 mmol\/L) or a high-glucose (30 mmol\/L) condition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcome Measures<\/jats:title><jats:p>Two weeks after treatment, we measured erectile function by electrical stimulation of the cavernous nerve and the penis was harvested for histologic studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Repeated intracavernous injections of rh-HGF protein induced significant restoration of erectile function in diabetic mice (89\u2013100% of control values), whereas a single intracavernous injection of rh-HGF protein elicited modest improvement. Rh-HGF significantly induced phosphorylation of its receptor c-Met, increased the content of endothelial cells and smooth muscle cells, and decreased the generation of reactive oxygen species (superoxide anion and peroxynitrite) and extravasation of oxidized low-density lipoprotein in diabetic mice. Under the high-glucose condition, rh-HGF protein also promoted tube formation in mouse cavernous endothelial cells and enhanced neurite sprouting in major pelvic ganglion culture in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The dual angiogenic and neurotrophic effects of HGF could open a new avenue through which diabetic erectile dysfunction can be treated.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.jsxm.2016.09.017","type":"journal-article","created":{"date-parts":[[2016,10,20]],"date-time":"2016-10-20T03:47:43Z","timestamp":1476935263000},"page":"1618-1628","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"title":["Effectiveness of Intracavernous Delivery of Recombinant Human Hepatocyte Growth Factor on Erectile Function in the Streptozotocin-Induced Diabetic Mouse"],"prefix":"10.1093","volume":"13","author":[{"given":"Nando Dulal","family":"Das","sequence":"first","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology , Incheon, , Republic of Korea"},{"name":"Inha University School of Medicine , Incheon, , Republic of Korea"},{"name":"Epigenetics Drug Discovery Unit , Yokohama, , Japan"},{"name":"Division of Structural and Synthetic Biology , Yokohama, , Japan"},{"name":"RIKEN Center for Life Science Technologies , Yokohama, , Japan"},{"name":"Suehiro-cho , Yokohama, , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo Nan","family":"Yin","sequence":"additional","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology , Incheon, , Republic of Korea"},{"name":"Inha University School of Medicine , Incheon, , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Ji","family":"Choi","sequence":"additional","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology , Incheon, , Republic of Korea"},{"name":"Inha University School of Medicine , Incheon, , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang-Moon","family":"Song","sequence":"additional","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology , Incheon, , Republic of Korea"},{"name":"Inha University School of Medicine , Incheon, , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Mi","family":"Park","sequence":"additional","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology , Incheon, , Republic of Korea"},{"name":"Inha University School of Medicine , Incheon, , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Limanjaya","sequence":"additional","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology , Incheon, , 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