{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:44:05Z","timestamp":1792212245191,"version":"4.4.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Klinikum der Universit\u00e4t M\u00fcnchen"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["World J Urol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Storage symptoms in overactive bladder are explained by detrusor contractions and bladder wall thickening. Arf6 and Rac1 are monomeric GTPases with newly emerging roles in smooth muscle contraction and proliferation. Here, we investigated human bladder smooth muscle cells (hBSMC) functions after silencing of Arf6 or Rac1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>hBSMC were transfected with Arf6- or Rac1-specific or scrambled siRNA (controls), and characterized using collagen contraction assays, for proliferation (EdU, Ki67), viability, growth in colony formation assays and actin organization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Arf6 and Rac1 silencing was confirmed by RT-PCR. Time-dependent contractions (0.5\u20136\u00a0h after assay initiation) were reduced in Arf6- and Rac1-silenced cells (36% Arf6, 28% Rac1, after 6\u00a0h), compared to scramble-transfected cells. Carbachol (3 \u00b5M) increased the time-dependent contractions, which were reduced by silencing of Arf6 (40\u201362%, 0.5\u20136\u00a0h) or Rac1 (30\u201359% at 0.5\u20136\u00a0h). With U46619 or endothelin-1, time-dependent contractions were similar to contractions without agonists, but again reduced in Arf6- and Rac1-silenced cells. Compared to scramble-transfected cells, silencing reduced the proliferation rate (Arf6 52%, Rac1 33%), Ki67 mRNA expression (89%, 91%), colony formation (63%, 66%), viability (Arf6 up to 84%, Rac1 up to 85%), and actin polymerization (30%, 31%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Arf6 and Rac1 promote time-dependent and carbachol-induced contractions of hBSMC, which may be mediated by actin polymerization. Simultaneously, Arf6 and Rac1 promote proliferation, growth and survival in hBSMC. Arf6 and Rac1 may be potentially involved in detrusor overactivity, bladder wall thickening and medical treatment of overactive bladder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00345-025-05652-y","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T09:44:45Z","timestamp":1746611085000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Silencing of Rac1 and Arf6 reduces time-dependent and carbachol-induced contractions, proliferation, survival and growth in human bladder smooth muscle cells"],"prefix":"10.1007","volume":"43","author":[{"given":"Siwei","family":"Qian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Tamalunas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian G.","family":"Stief","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hennenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"issue":"4","key":"5652_CR1","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1124\/pharmrev.121.000523","volume":"75","author":"MC Michel","year":"2023","unstructured":"Michel MC, Cardozo L, Chermansky CJ, Cruz F, Igawa Y, Lee KS et al (2023) Current and emerging Pharmacological targets and treatments of urinary incontinence and related disorders. 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The study was performed in commercially available cells.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable. The study was performed in commercially available cells.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Patient consent statement"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"279"}}