{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T07:14:43Z","timestamp":1781075683028,"version":"3.54.1"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2014,5,6]],"date-time":"2014-05-06T00:00:00Z","timestamp":1399334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK087872"],"award-info":[{"award-number":["R01DK087872"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:p>\n                    Men with sickle cell disease (SCD) risk developing priapism. Recognizing that SCD is a disease of hypoxia, we investigated the effect of hypoxia on gene expression in corporal smooth muscle (CSM) cells. Rat CSM cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    were treated with CoCl\n                    <jats:sub>2<\/jats:sub>\n                    or low oxygen tension to mimic hypoxia. Hypoxic conditions increased expression of genes previously associated with priapism in animal models. Variable coding sequence a1\n                    <jats:italic>(Vcsa1;<\/jats:italic>\n                    the rat opiorphin homologue, sialorphin), hypoxia\u2010inducible factor 1a\n                    <jats:italic>(Hif\u20101a)<\/jats:italic>\n                    , and A2B adenosine receptor\n                    <jats:italic>(a2br)<\/jats:italic>\n                    were increased by 10\u2010, 4\u2010, and 6\u2010fold, respectively, by treatment with CoCl\n                    <jats:sub>2<\/jats:sub>\n                    , whereas low oxygen tension caused increases in expression of 3\u2010, 4\u2010, and 1.5\u2010fold, respectively. Sialorphin\u2010treated CSM cells increased expression of\n                    <jats:italic>Hif\u20101a<\/jats:italic>\n                    and\n                    <jats:italic>a2br<\/jats:italic>\n                    by 4\u2010fold, and\n                    <jats:italic>vcsa1\u2010siRNA<\/jats:italic>\n                    treatment reduced expression by ~50%. Using a Hif\u20101a inhibitor, we demonstrated up\u2010regulation of\n                    <jats:italic>a2br<\/jats:italic>\n                    by sialorphin is dependent on\n                    <jats:italic>Hif\u20101a<\/jats:italic>\n                    , and knockdown of\n                    <jats:italic>vcsa1<\/jats:italic>\n                    expression with\n                    <jats:italic>vcsa1<\/jats:italic>\n                    \u2010si\n                    <jats:italic>RNA<\/jats:italic>\n                    demonstrated that hypoxic\u2010upregulation of\n                    <jats:italic>Hif\u20101a<\/jats:italic>\n                    is dependent on\n                    <jats:italic>vcsa1.<\/jats:italic>\n                    In CSM from a SCD mouse, there was 15\u2010fold up\u2010regulation of opiorphin at a life stage prior to priapism. We conclude that in CSM, opiorphins are master regulators of the hypoxic response. Opiorphin up\u2010regulation in response to SCD\u2010associated hypoxia activates CSM \u201crelaxant\u201d pathways; excessive activation of these pathways results in priapism.\u2014Fu, S., Tar, M. T., Melman, A., Davies, K. P. Opiorphin is a master regulator of the hypoxic response in corporal smooth muscle cells.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    28, 3633\u20133644 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-248708","type":"journal-article","created":{"date-parts":[[2014,5,7]],"date-time":"2014-05-07T00:35:43Z","timestamp":1399422943000},"page":"3633-3644","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Opiorphin is a master regulator of the hypoxic response in corporal smooth muscle cells"],"prefix":"10.1096","volume":"28","author":[{"given":"Shibo","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Urology Albert Einstein College of Medicine Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moses Tarndie","family":"Tar","sequence":"additional","affiliation":[{"name":"Department of Urology Albert Einstein College of Medicine Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold","family":"Melman","sequence":"additional","affiliation":[{"name":"Department of Urology Albert Einstein College of Medicine Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin Paul","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Urology Albert Einstein College of Medicine Bronx New York USA"},{"name":"Department of Physiology and Biophysics Albert Einstein College of Medicine Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,5,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1980.00330220022011"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-194807000-00002"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7262.2008.00314.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21475"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2011.02288.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1378650"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-228817"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2008.01187.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00656.2008"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33467"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1111\/j.1743-6109.2009.01552.x","article-title":"Adenosine deaminase enzyme therapy prevents and reverses the heightened cavernosal relaxation in priapism","volume":"9","author":"Wen J.","year":"2010","journal-title":"J. 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