{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:45:55Z","timestamp":1786977955509,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"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":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Studies regarding age\u2010related erectile dysfunction (ED) based on naturally aging models are limited by their high costs, especially for the acquisition of primary cells from the corpus cavernosum. Herein,\n                    <jats:sc>d<\/jats:sc>\n                    \u2010galactose (\n                    <jats:sc>d<\/jats:sc>\n                    \u2010gal) was employed to accelerate cell senescence, and the underlying mechanism was explored. As predominant functional cells involved in the erectile response, corpus cavernosum smooth muscle cells (CCSMCs) were isolated from 2\u2010month\u2010old rats. Following this,\n                    <jats:sc>d<\/jats:sc>\n                    \u2010gal was introduced to induce cell senescence, which was verified via \u03b2\u2010galactosidase staining. The effects of\n                    <jats:sc>d<\/jats:sc>\n                    \u2010gal on CCSMCs were evaluated by terminal deoxynucleoitidyl transferase dUTP nick\u2010end labeling (TUNEL), immunofluorescence staining, flow cytometry, western blot, and quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR). Furthermore, RNA interference (RNAi) was carried out for rescue experiments. Subsequently, the influence of senescence on the corpus cavernosum was determined via scanning electron microscopy, qRT\u2010PCR, immunohistochemistry, TUNEL, and Masson stainings. The results revealed that the accelerated senescence of CCSMCs was promoted by\n                    <jats:sc>d<\/jats:sc>\n                    \u2010gal. Simultaneously, smooth muscle alpha\u2010actin (alpha\u2010SMA) expression was inhibited, while that of osteopontin (OPN) and Kr\u00fcppel\u2010like factor 4 (KLF4), as well as fibrotic and apoptotic levels, were elevated. After knocking down KLF4 expression in\n                    <jats:sc>d<\/jats:sc>\n                    \u2010gal\u2010induced CCSMCs by RNAi, the expression level of cellular alpha\u2010SMA increased. Contrastingly, the OPN expression, apoptotic and fibrotic levels declined. In addition, cellular senescence acquired partial remission. Accordingly, in the aged corpus cavernosum, the fibrotic and apoptotic rates were increased, followed by downregulation in the expression of alpha\u2010SMA and the concurrent upregulation in the expression of OPN and KLF4. Overall, our results signaled that\n                    <jats:sc>d<\/jats:sc>\n                    \u2010gal\u2010induced accelerated senescence of CCSMCs could trigger fibrosis, apoptosis and phenotypic switch to the synthetic state, potentially attributed to the upregulation of KLF4 expression, which may be a multipotential therapeutic target of age\u2010related ED.\n                  <\/jats:p>","DOI":"10.1002\/jcp.31150","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T06:19:41Z","timestamp":1699510781000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>d<\/scp>\n                    \u2010Galactose induces the senescence and phenotype switch of corpus cavernosum smooth muscle cells"],"prefix":"10.1002","volume":"239","author":[{"given":"Daoyuan","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Urology The Sixth Affiliated Hospital, Sun Yat\u2010Sen University Guangzhou China"},{"name":"Biomedical Innovation Center The Sixth Affiliated Hospital, Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Urology The Third Affiliated Hospital, Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Urology The Sixth Affiliated Hospital, Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Urology The Third Affiliated Hospital, Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department 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