{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T18:04:08Z","timestamp":1770487448874,"version":"3.49.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"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":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education","award":["2017R1A6A3A11030261"],"award-info":[{"award-number":["2017R1A6A3A11030261"]}]},{"name":"Medical Research Center","award":["2014R1A5A2009392"],"award-info":[{"award-number":["2014R1A5A2009392"]}]},{"name":"Korean government"}],"content-domain":{"domain":["jsm.jsexmed.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,3,1]]},"abstract":"Abstract<\/jats:title>\n \n Introduction<\/jats:title>\n Penile neurovascular dysfunction is a major cause of erectile dysfunction (ED) in diabetic patients, which causes poor response to oral phosphodiesterase-5 inhibitors. Nerve growth factor precursor (proNGF) and its p75 neurotrophin receptor (p75NTR) have been known to be involved in microvascular complications and neurodegeneration.<\/jats:p>\n <\/jats:sec>\n \n Aim<\/jats:title>\n To examine the role of proNGF and its receptor p75NTR signaling pathway in diabetic ED, and to determine the effectiveness of proNGF neutralizing antibody (proNGF-Ab) in restoring erectile function in streptozotocin (STZ)-induced diabetic mice.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Diabetes mellitus was induced by intraperitoneal injection of STZ (50 mg\/kg) into 8-week-old C57BL\/6 male mice for 5 consecutive days. At 8 weeks after the induction of diabetes mellitus, the animals were distributed into 3 groups: controls and STZ-induced diabetic mice receiving 2 intracavernous injections of either saline (days\u00a0\u22123 and 0; 20 \u03bcL) or proNGF-Ab (days\u00a0\u22123 and 0; 20 \u03bcg in 20 \u03bcL of saline). We also examined the effect of proNGF-Ab or p75NTR small interfering RNA in primary cultured mouse cavernous endothelial cells, pericytes, and major pelvic ganglion.<\/jats:p>\n <\/jats:sec>\n \n Main Outcome Measures<\/jats:title>\n Erectile function was measured by electrical stimulation of the cavernous nerve at 2 weeks after treatment, and the penis was then harvested for histologic and biochemical studies.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The cavernous expression of proNGF and p75NTR was upregulated under diabetic conditions. Intracavernous injection of proNGF-Ab successfully restored erectile function in diabetic mice, which reach 93\u201396% of control values. ProNGF-Ab significantly restored cavernous endothelial cell, pericyte, and neuronal cell content, and increased endothelial cell-to-cell junction proteins in the diabetic mice. Under the high-glucose condition, proNGF-Ab or p75NTR small interfering RNA promoted tube formation in mouse cavernous endothelial cells and pericytes, decreased apoptosis of endothelial cells and pericytes, and enhanced neurite sprouting from major pelvic ganglion.<\/jats:p>\n <\/jats:sec>\n \n Clinical Implications<\/jats:title>\n The ProNGF\/p75NTR pathway will be a new therapeutic target for diabetic ED.<\/jats:p>\n <\/jats:sec>\n \n Strength & Limitations<\/jats:title>\n This is the first study demonstrating the efficacy of the inhibition of proNGF\/p75NTR pathway in diabetic ED. Further studies are needed to test whether a different dosing of proNGF-Ab would induce more durable erectile function recovery.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Our findings suggest that inhibition of the proNGF\/p75NTR signaling pathway is a promising therapeutic strategy for diabetic ED.<\/jats:p>\n <\/jats:sec>","DOI":"10.1016\/j.jsxm.2019.01.013","type":"journal-article","created":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T18:16:15Z","timestamp":1551723375000},"page":"351-364","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"title":["Inhibition of proNGF and p75NTR Pathway Restores Erectile Function Through Dual Angiogenic and Neurotrophic Effects in the Diabetic Mouse"],"prefix":"10.1093","volume":"16","author":[{"given":"Nhat Minh","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang-Moon","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Ji","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalyan","family":"Ghatak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi-Hye","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiyeon","family":"Ock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo 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