{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T14:30:56Z","timestamp":1768314656985,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T00:00:00Z","timestamp":1643760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The main pathophysiologic conditions of erectile dysfunction (ED) after radical prostatectomy are considered to be corporal fibrosis and apoptosis induced by cavernosal nerve (CN) injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>In a rat model of CN crush injury (CNCI), we investigated whether combination treatment with JNK inhibitor (JNKi), SP600125, and HDAC inhibitor (HDACi), suberoylanilide\u2010hydroxamic\u20107 acid (SAHA), for 2\u00a0weeks after CNCI would restore erectile function by suppressing fibrosis and apoptosis through normalization of JNK and HDAC pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Seventy 12\u2010week\u2010old rats were randomly divided into five groups: Sham surgery, CNCI alone, CNCI treated with daily intraperitoneal injection of 10\u00a0mg\/kg JNKi, CNCI treated with daily oral administration of 25.0\u00a0mg\/kg HDACi, and CNCI daily treated with a combination. Two weeks after CNCI, we investigated the erectile response to electrostimulation and conducted histological staining, caspase\u20103 activity assay, and western blot analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CNCI alone resulted in significantly reduced intracavernosal pressure\/mean arterial pressure (MAP) and area under the curve\/MAP, decreased smooth muscle (SM)\/collagen ratio and SM content, higher caspase\u20103 activity, and increased protein levels of total HDAC3, transforming growth factor (TGF)\u2010\u03b2, fibronectin, and c\u2010Jun phosphorylation, compared with the Sham surgery. The CNCI groups exposed to JNKi, HDACi or both showed improvements in erectile\u2010responses and SM\/collagen ratio, compared to the CNCI alone. The combined treatment showed additional improvement in erectile responses at 1.0V stimulation and in SM\/collagen ratio compared to the single agent treatment. SM content, caspase\u20103 activity, and c\u2010Jun phosphorylation improved in the two CNCI groups exposed to JNKi. The two CNCI groups exposed to HDACi showed normalization of protein levels of HDAC3, fibronectin, and TGF\u2010\u03b2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and conclusions<\/jats:title><jats:p>The combined administration of JNKi and HDACi during the acute phase after CNCI in rats can preserve ED by suppressing cavernosal fibrosis and apoptosis by normalizing the HDAC\/TGF\u2010\u03b2 and JNK pathways.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13154","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T04:37:08Z","timestamp":1642048628000},"page":"758-766","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Restoring erectile function by combined treatment with JNK inhibitor and HDAC inhibitor in a rat model of cavernous nerve injury"],"prefix":"10.1111","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8330-0329","authenticated-orcid":false,"given":"Junghoon","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Urology Seoul National University Boramae Medical Center Seoul National University College of Medicine  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7288-1706","authenticated-orcid":false,"given":"Min Chul","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Urology Seoul National University Boramae Medical Center Seoul National University College of Medicine  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5033-0153","authenticated-orcid":false,"given":"Hwancheol","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Urology Seoul National University Boramae Medical Center Seoul National University College of Medicine  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5519-2490","authenticated-orcid":false,"given":"Soo Woong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Urology Seoul National University Hospital Seoul National University College of Medicine  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,2,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21590"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.2996"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2019.0023"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2011.09.051"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2009.08419.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209978"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.5534\/wjmh.2016.34.2.73"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000048974.47461.50"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2008.01105.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.12228"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450116666150202153832"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091327"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.301"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2012.01.016"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2017.11.040"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2007.05.016"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12922"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.4103\/aja.aja_82_17"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2008.01.032"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOU.0b013e3283136462"},{"issue":"1","key":"e_1_2_9_22_1","first-page":"31","article-title":"Is it possible to recover erectile function spontaneously after cavernous nerve injury? 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