{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T19:25:23Z","timestamp":1761765923262},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004332","name":"Seoul National University Hospital","doi-asserted-by":"publisher","award":["03-2011-0552"],"award-info":[{"award-number":["03-2011-0552"]}],"id":[{"id":"10.13039\/501100004332","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>The molecular mechanism of corporal fibrosis leading to erectile dysfunction (ED) following cavernous nerve (CN) injury is poorly understood.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>To determine whether the LIMK2\/cofilin pathway, the downstream effectors of ROCK1, was involved in ED and corporal fibrosis following bilateral CN injury in male rats.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Forty-eight 10-week-old male Sprague-Dawley rats were equally divided into three groups: sham surgery (S); bilateral CN crush injury (I); and bilateral CN resection (R). Within each groups, two subgroups were analyzed at 1 and 4 weeks postoperatively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>Electrostimulation was performed to assess erectile function by the ratio of maximal intracavernous pressure to mean arterial pressure (ICP\/MAP) and areas under the ICP curve to MAP (AUC\/MAP). Penile tissue was processed for Masson's trichrome staining, Western blot (ROCK1, total LIMK2, phospho-LIMK2, total cofilin, phospho-cofilin), immunohistochemistry (alpha-SM actin [\u03b1-SMA]), and double immunofluorescent staining (ROCK1, phospho-LIMK2, vimentin).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>At each time point, both I and R groups showed a significantly lower percent of ICP\/MAP and AUC, and decreased SM cell\/collagen ratio and expression of \u03b1-SMA than S group. Densitometry revealed a significantly higher expression of ROCK1 in I and R groups compared with S group at all time points. The LIMK2 phosphorylation in I and R groups significantly increased at 1 week, but not at 4 weeks. The cofilin phosphorylation in R group significantly increased to that in S group starting at 1 week, while that in I group was increased significantly at 4 weeks. The double immunofluorescent staining noted that coexpression of vimentin with ROCK1 or phospho-LIMK2 in I and R groups was significantly increased mainly in the subtunical area at 1 week but not at 4 weeks.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The ROCK1\/LIMK2\/cofilin pathway may be involved in ED related to corporal fibrosis, and it appears to be functional particularly in the early period after CN injury.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jsm.12903","type":"journal-article","created":{"date-parts":[[2015,4,28]],"date-time":"2015-04-28T08:54:21Z","timestamp":1430211261000},"page":"1522-1532","source":"Crossref","is-referenced-by-count":33,"title":["Involvement of Rho-Kinase\/LIM Kinase\/Cofilin Signaling Pathway in Corporal Fibrosis after Cavernous Nerve Injury in Male Rats"],"prefix":"10.1093","volume":"12","author":[{"given":"Sang Hoon","family":"Song","sequence":"first","affiliation":[{"name":"Department of Urology , Seoul, \u00a0 South Korea"},{"name":"Asan Medical Center , Seoul, \u00a0 South Korea"},{"name":"College of Medicine , Seoul, \u00a0 South Korea"},{"name":"University of Ulsan , Seoul, \u00a0 South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwanjin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Urology , Seoul, \u00a0 South Korea"},{"name":"Seoul National University Hospital , Seoul, \u00a0 South Korea"},{"name":"College of Medicine , Seoul, \u00a0 South Korea"},{"name":"University of Seoul , Seoul, \u00a0 South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo Woong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Urology , Seoul, \u00a0 South Korea"},{"name":"Seoul National University Hospital , Seoul, \u00a0 South Korea"},{"name":"College of Medicine , Seoul, \u00a0 South Korea"},{"name":"University of Seoul , Seoul, \u00a0 South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Seung","family":"Paick","sequence":"additional","affiliation":[{"name":"Department of Urology , Seoul, \u00a0 South Korea"},{"name":"Seoul National University Hospital , Seoul, \u00a0 South Korea"},{"name":"College of Medicine , Seoul, \u00a0 South Korea"},{"name":"University of Seoul , Seoul, \u00a0 South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Chul","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Urology , Goyang, \u00a0 South Korea"},{"name":"College of Medicine , Goyang, \u00a0 South Korea"},{"name":"Dongguk University , Goyang, \u00a0 South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,7,1]]},"reference":[{"key":"2023010713352156800_bb0010","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.eururo.2012.05.046","article-title":"Systematic review and meta-analysis of studies reporting potency rates after robot-assisted radical prostatectomy","volume":"62","author":"Ficarra","year":"2012","journal-title":"Eur Urol"},{"key":"2023010713352156800_bb0015","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1111\/j.1743-6109.2008.00955.x","article-title":"Cavernous nerve injury using rodent animal models","volume":"5","author":"Canguven","year":"2008","journal-title":"J Sex Med"},{"key":"2023010713352156800_bb0020","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1097\/MOU.0b013e3283136462","article-title":"Penile rehabilitation following radical prostatectomy","volume":"18","author":"Mulhall","year":"2008","journal-title":"Curr Opin Urol"},{"key":"2023010713352156800_bb0025","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1097\/01.ju.0000048974.47461.50","article-title":"Penile weight and cell subtype specific changes in a post-radical prostatectomy model of erectile dysfunction","volume":"169","author":"User","year":"2003","journal-title":"J Urol"},{"key":"2023010713352156800_bb0030","first-page":"185","article-title":"Relationship between venous incompetence and cavernous nerve injury: Ultrastructural alteration of cavernous smooth muscle in the neurotomized dog","volume":"3","author":"Paick","year":"1991","journal-title":"Int J Impotence Res"},{"key":"2023010713352156800_bb0035","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/sj.ijir.3900328","article-title":"Is there a role of hypoxemia in penile fibrosis: A viewpoint presented to the Society for the Study of Impotence","volume":"10","author":"Moreland","year":"1998","journal-title":"Int J Impot Res"},{"key":"2023010713352156800_bb0040","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1016\/j.febslet.2006.04.033","article-title":"The logic of TGFbeta signaling","volume":"580","author":"Massague","year":"2006","journal-title":"FEBS Lett"},{"key":"2023010713352156800_bb0045","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1111\/j.1742-4658.2009.07031.x","article-title":"Control of transforming growth factor beta signal transduction by small GTPases","volume":"276","author":"Kardassis","year":"2009","journal-title":"FEBS J"},{"key":"2023010713352156800_bb0050","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1111\/j.1743-6109.2010.02147.x","article-title":"Involvement of sphingosine-1-phosphate\/RhoA\/Rho-kinase signaling pathway in corporal fibrosis following cavernous nerve injury in male rats","volume":"8","author":"Cho","year":"2011","journal-title":"J Sex Med"},{"key":"2023010713352156800_bb0055","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.neuroscience.2008.05.027","article-title":"Reflex penile erection in anesthetized mice: an exploratory study","volume":"155","author":"Allard","year":"2008","journal-title":"Neuroscience"},{"key":"2023010713352156800_bb0060","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1111\/j.1743-6109.2010.01724.x","article-title":"Chronic treatment with an oral rho-kinase inhibitor restores erectile function by suppressing corporal apoptosis in diabetic rats","volume":"8","author":"Li","year":"2011","journal-title":"J Sex Med"},{"key":"2023010713352156800_bb0065","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1111\/j.1743-6109.2012.02720.x","article-title":"Investigation of the effects of the level of glycemic control on erectile function and pathophysiological mechanisms in diabetic rats","volume":"9","author":"Cho","year":"2012","journal-title":"J Sex Med"},{"key":"2023010713352156800_bb0070","doi-asserted-by":"crossref","first-page":"11448","DOI":"10.1074\/jbc.M402651200","article-title":"LIM-kinase 2 and cofilin phosphorylation mediate actin cytoskeleton reorganization induced by transforming growth factor-beta","volume":"280","author":"Vardouli","year":"2005","journal-title":"J Biol Chem"},{"key":"2023010713352156800_bb0075","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/jcp.21424","article-title":"Rho plays a key role in TGF-beta1-induced cytoskeletal rearrangement in human retinal pigment epithelium","volume":"216","author":"Lee","year":"2008","journal-title":"J Cell Physiol"},{"key":"2023010713352156800_bb0080","doi-asserted-by":"crossref","first-page":"657","DOI":"10.2217\/fca.11.51","article-title":"Rho kinase as a therapeutic target in cardiovascular disease","volume":"7","author":"Surma","year":"2011","journal-title":"Future Cardiol"},{"key":"2023010713352156800_bb0085","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1016\/j.juro.2010.06.094","article-title":"Activated RhoA\/Rho kinase impairs erectile function after cavernous nerve injury in rats","volume":"184","author":"Gratzke","year":"2010","journal-title":"J Urol"},{"key":"2023010713352156800_bb0090","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1093\/cvr\/cvp135","article-title":"Rho kinase-1 mediates cardiac fibrosis by regulating fibroblast precursor cell differentiation","volume":"83","author":"Haudek","year":"2009","journal-title":"Cardiovasc Res"},{"key":"2023010713352156800_bb0095","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1096\/fj.05-5129com","article-title":"Targeted deletion of ROCK1 protects the heart against pressure overload by inhibiting reactive fibrosis","volume":"20","author":"Zhang","year":"2006","journal-title":"FASEB J"},{"key":"2023010713352156800_bb0100","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/j.1743-6109.2008.01105.x","article-title":"Fibrosis and loss of smooth muscle in the corpora cavernosa precede corporal veno-occlusive dysfunction (CVOD) induced by experimental cavernosal nerve damage in the rat","volume":"6","author":"Ferrini","year":"2009","journal-title":"J Sex Med"},{"key":"2023010713352156800_bb0105","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s00109-007-0165-6","article-title":"LIM kinases: Function, regulation and association with human disease","volume":"85","author":"Scott","year":"2007","journal-title":"J Mol Med (Berl)"},{"key":"2023010713352156800_bb0110","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1042\/bj3540149","article-title":"LIM-kinase 2 induces formation of stress fibres, focal adhesions and membrane blebs, dependent on its activation by Rho-associated kinase-catalysed phosphorylation at threonine-505","volume":"354","author":"Amano","year":"2001","journal-title":"Biochem J"},{"key":"2023010713352156800_bb0115","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.vph.2005.11.008","article-title":"Upregulation of profilin, cofilin-2 and LIMK2 in cultured pulmonary artery smooth muscle cells and in pulmonary arteries of monocrotaline-treated rats","volume":"44","author":"Dai","year":"2006","journal-title":"Vascul Pharmacol"},{"key":"2023010713352156800_bb0120","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ejcb.2010.09.009","article-title":"Differing contributions of LIMK and ROCK to TGFbeta-induced transcription, motility and invasion","volume":"90","author":"Morin","year":"2011","journal-title":"Eur J Cell Biol"}],"container-title":["The Journal of Sexual Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1743609515341655?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1743609515341655?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/12\/7\/1522\/48476141\/jsm_12_7_1522.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/12\/7\/1522\/48476141\/jsm_12_7_1522.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T14:42:54Z","timestamp":1675953774000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jsm\/article\/12\/7\/1522\/6966836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,1]]},"references-count":23,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2015,7,1]]},"published-print":{"date-parts":[[2015,7,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jsm.12903","relation":{},"ISSN":["1743-6109","1743-6095"],"issn-type":[{"value":"1743-6109","type":"electronic"},{"value":"1743-6095","type":"print"}],"subject":[],"published-other":{"date-parts":[[2015,7]]},"published":{"date-parts":[[2015,7,1]]}}}