{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T19:05:07Z","timestamp":1788548707516,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82360155"],"award-info":[{"award-number":["82360155"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20202BABL206031,20224BAB216024"],"award-info":[{"award-number":["20202BABL206031,20224BAB216024"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The etiology of chronic prostatitis remains unclear; consequently, this disease is associated with recurrence and ineffective clinical therapy. Therefore, there is an urgent need to investigate the underlying pathogenesis of chronic prostatitis in order to develop more efficacious treatments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The previous study found that knocking out of PEBP4 leads to chronic prostatitis in the male mice. This research aimed to identify the role of PEBP4 in prostatitis, determine the molecular pathogenic mechanisms associated with chronic prostatitis, and provide guidelines for the development of new treatment strategies for chronic prostatitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      A\n                      <jats:italic>PEBP4<\/jats:italic>\n                      exon knockout strain (\n                      <jats:italic>\n                        PEBP4\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      ) was established in C57BL\/6 mice via the Cre\u2010loxP system. Hematoxylin\u2010eosin (H&amp;E) staining was used to investigate histological changes. RNA\u2010sequencing was used to investigate the gene expression signature of the prostate and the levels of inflammatory cytokines were determined by real\u2010time polymerase chain reaction (RT\u2010PCR). The expression of PEBP4 protein in prostate tissue was determined by immunohistochemistry in specimens from patients with BPH and BPH combined with chronic prostatitis. Finally, we used a CRISPR\u2010Cas9 plasmid to knockout\n                      <jats:italic>PEBP4<\/jats:italic>\n                      in RWPE\u20101 cells; western blotting was subsequently used to measure the level of activation in the NF\u2010\u03baB signaling pathway after activating with TNF\u2010\u03b1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Hemorrhage and inflammatory cell infiltration were incidentally observed in the seminal vesicles and prostate glands of\n                      <jats:italic>PEBP4<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice after being fed with a normal diet for 1 year. In addition, we found significantly lower (\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      &lt;\u00a00.001) expression levels of PEBP4 protein in prostate tissues from patients with benign prostate hyperplasia (BPH) and chronic and non\u2010bacterial prostatitis (CNP)\u00a0when compared to those with BPH only. The reduced expression of PEBP4 led to a higher risk of prostatitis recurrence in patients after 2 years of follow\u2010up. Increased levels of NF\u2010\u03baB and I\u03baB phosphorylation were observed in\n                      <jats:italic>PEBP4<\/jats:italic>\n                      \u2010knockout RWPE\u20101 cells and prostate glands from\n                      <jats:italic>PEBP4<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The knockout of\n                      <jats:italic>PEBP4<\/jats:italic>\n                      in experimental mice led to chronic prostatitis and the reduced expression of PEBP4 in patients with higher risk of chronic and non\u2010bacterial prostatitis suggested that PEBP4 might act as a protective factor against chronic prostatitis. The knockout of\n                      <jats:italic>PEBP4<\/jats:italic>\n                      in RWPE\u20101 cells led to the increased activation of NF\u2010\u03baB and I\u03baB, thus indicating that inhibition of PEBP4 faciliated the NF\u2010\u03baB signaling cascade. Our findings provide a new etiology and therapeutic target for chronic prostatitis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.13647","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T04:33:03Z","timestamp":1712637183000},"page":"331-341","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Knockout of phosphatidylethanolamine binding protein4 (\n                    <i>PEBP4<\/i>\n                    ) promotes chronic non\u2010bacterial prostatitis by mediating the activation of NF\u2010\u03baB signaling"],"prefix":"10.1111","volume":"13","author":[{"given":"Hailan","family":"He","sequence":"first","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Gannan Medical University Ganzhou Jiangxi China"},{"name":"Institute of Urology The First Affiliated Hospital of Gannan Medical University Ganzhou Jiangxi 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