{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T03:35:33Z","timestamp":1762659333331,"version":"build-2065373602"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,8,13]],"date-time":"2014-08-13T00:00:00Z","timestamp":1407888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004084","name":"Korea Science and Engineering Foundation","doi-asserted-by":"crossref","award":["2011-0015771"],"award-info":[{"award-number":["2011-0015771"]}],"id":[{"id":"10.13039\/501100004084","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Korea government (Ministry for Education, Science, and Technology)"}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To examine the therapeutic effect of adenovirus encoding histone deacetylase 2 (\n                      <jats:styled-content style=\"fixed-case\">HDAC2<\/jats:styled-content>\n                      ) small hairpin\n                      <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                      (\n                      <jats:styled-content style=\"fixed-case\">Ad\u2010HDAC2 shRNA<\/jats:styled-content>\n                      ) in a rat model of\n                      <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\n                      eyronie's disease (\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      ) and to determine the mechanisms by which\n                      <jats:styled-content style=\"fixed-case\">HDAC2<\/jats:styled-content>\n                      knockdown ameliorates fibrotic responses in primary fibroblasts derived from human\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      plaque.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Rats were distributed into four groups (\n                      <jats:italic>n<\/jats:italic>\n                      = 6 per group): age\u2010matched controls without treatment; rats in which\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      has been induced (\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      rats) without treatment;\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      rats receiving a single injection of control adenovirus encoding scrambled small hairpin RNA\n                      <jats:styled-content style=\"fixed-case\">(Ad\u2010shRNA<\/jats:styled-content>\n                      ) (day 15; 1 \u00d7 10\n                      <jats:sup>8<\/jats:sup>\n                      pfu\/0.1\u2009mL phosphate\u2010buffered saline [\n                      <jats:styled-content style=\"fixed-case\">PBS<\/jats:styled-content>\n                      ]); and\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      rats receiving a single injection of\n                      <jats:styled-content style=\"fixed-case\">Ad\u2010HDAC2 shRNA<\/jats:styled-content>\n                      (day 15; 1 \u00d7 10\n                      <jats:sup>8<\/jats:sup>\n                      pfu\/0.1\u2009mL\n                      <jats:styled-content style=\"fixed-case\">PBS<\/jats:styled-content>\n                      ) into the lesion.\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      \u2010like plaque was induced by repeated intratunical injections of 100 \u03bcL each of human fibrin and thrombin solutions on days 0 and 5. On day 30, the penis was harvested for histological examination. Fibroblasts isolated from human\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      plaque were pretreated with\n                      <jats:styled-content style=\"fixed-case\">HDAC2<\/jats:styled-content>\n                      small interfering (si)\n                      <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                      (100 pmoL) and then stimulated with transforming growth factor (\n                      <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n                      )\u2010\u03b21 (10\u2009ng\/mL) to determine hydroxyproline levels, procollagen\n                      <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                      , apoptosis and protein expression of poly(\n                      <jats:styled-content style=\"fixed-case\">ADP<\/jats:styled-content>\n                      \u2010ribose) polymerase 1 (\n                      <jats:styled-content style=\"fixed-case\">PARP1<\/jats:styled-content>\n                      ) and cyclin\n                      <jats:styled-content style=\"fixed-case\">D1<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We observed that\n                      <jats:styled-content style=\"fixed-case\">Ad\u2010HDAC2 shRNA<\/jats:styled-content>\n                      decreased inflammatory cell infiltration, reduced transnuclear expression of phospho\u2010\n                      <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>\n                      mad3 and regressed fibrotic plaque of the tunica albuginea in\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      rats\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                      <jats:styled-content style=\"fixed-case\">siRNA<\/jats:styled-content>\n                      \u2010mediated silencing of\n                      <jats:styled-content style=\"fixed-case\">HDAC2<\/jats:styled-content>\n                      significantly decreased the\n                      <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\n                      \u2010\u03b21\u2010induced transdifferentiation of fibroblasts into myofibroblasts and collagen production, and induced apoptosis by downregulating the expression of\n                      <jats:styled-content style=\"fixed-case\">PARP1<\/jats:styled-content>\n                      , and decreased the expression of cyclin\n                      <jats:styled-content style=\"fixed-case\">D1<\/jats:styled-content>\n                      (a positive cell\u2010cycle regulator) in primary cultured fibroblasts derived from human\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      plaque\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Specific inhibition of\n                      <jats:styled-content style=\"fixed-case\">HDAC2<\/jats:styled-content>\n                      with\n                      <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                      interference may represent a novel targeted therapy for\n                      <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  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