{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:35:05Z","timestamp":1768509305071,"version":"3.49.0"},"posted":{"date-parts":[[2023,11,14]]},"group-title":"Cell Biology","reference-count":70,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,11,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Injury to contractile organs such as the heart, vasculature, urinary bladder and gut can stimulate a pathological response that results in loss of normal contractility. PDGF and TGF\u03b2 are among the most well studied initiators of the injury response and have been shown to induce aberrant contraction in mechanically active cells of hollow organs including smooth muscle cells (SMC) and fibroblasts. However the mechanisms driving contractile alterations downstream of PDGF and TGF\u03b2 in SMC and fibroblasts are incompletely understood, limiting therapeutic interventions. To identify potential molecular targets, we have leveraged the analysis of publicly available data, comparing transcriptomic changes in mechanically active cells stimulated with PDGF and TGF\u03b2 and identified a shared molecular profile regulated by MYC and members of the AP-1 transcription factor complex. We also analyzed data sets from SMC and fibroblasts treated in the presence or absence of the MYC inhibitor JQ1. This analysis revealed a unique set of cytoskeleton-associated genes that were sensitive to MYC inhibition. JQ1 was also able to attenuate TGF\u03b2 and PDGF induced changes to the cytoskeleton and contraction of smooth muscle cells and fibroblasts\n                  <jats:italic>in vitro<\/jats:italic>\n                  . These findings identify MYC as a key driver of aberrant cytoskeletal and contractile changes in fibroblasts and SMC, and suggest that JQ1 could be used to restore normal contractile function in hollow organs.\n                <\/jats:p>","DOI":"10.1101\/2023.11.14.567076","type":"posted-content","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T18:30:14Z","timestamp":1699986614000},"source":"Crossref","is-referenced-by-count":0,"title":["Investigation of the impact of bromodomain inhibition on cytoskeleton stability and contraction"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1388-6149","authenticated-orcid":false,"given":"Alexander","family":"Bigger-Allen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9625-6259","authenticated-orcid":false,"given":"Ali Hashemi","family":"Gheinani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0943-6236","authenticated-orcid":false,"given":"Rosalyn M.","family":"Adam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023111621001275000_2023.11.14.567076v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2009.09.020"},{"key":"2023111621001275000_2023.11.14.567076v1.2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00253.2008"},{"key":"2023111621001275000_2023.11.14.567076v1.3","doi-asserted-by":"crossref","first-page":"C294","DOI":"10.1152\/ajpcell.1999.277.2.C294","article-title":"AP-1 mediates stretch-induced expression of HB-EGF in bladder smooth muscle cells","volume":"277","year":"1999","journal-title":"Am J Physiol"},{"key":"2023111621001275000_2023.11.14.567076v1.4","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00181.2004"},{"key":"2023111621001275000_2023.11.14.567076v1.5","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090772"},{"key":"2023111621001275000_2023.11.14.567076v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.08.034"},{"key":"2023111621001275000_2023.11.14.567076v1.7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053430"},{"key":"2023111621001275000_2023.11.14.567076v1.8","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-014-0044-z"},{"key":"2023111621001275000_2023.11.14.567076v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(88)90337-5"},{"key":"2023111621001275000_2023.11.14.567076v1.10","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25879"},{"key":"2023111621001275000_2023.11.14.567076v1.11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005505200"},{"key":"2023111621001275000_2023.11.14.567076v1.12","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000255559.77687.c1"},{"key":"2023111621001275000_2023.11.14.567076v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210194"},{"key":"2023111621001275000_2023.11.14.567076v1.14","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-008-0279-5"},{"key":"2023111621001275000_2023.11.14.567076v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.134"},{"key":"2023111621001275000_2023.11.14.567076v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2047"},{"key":"2023111621001275000_2023.11.14.567076v1.17","doi-asserted-by":"publisher","DOI":"10.4161\/cc.24164"},{"key":"2023111621001275000_2023.11.14.567076v1.18","doi-asserted-by":"crossref","first-page":"101163","DOI":"10.1016\/j.redox.2019.101163","article-title":". c-MYC activation promotes cofilin-mediated F-actin cytoskeleton remodeling and telomere homeostasis as a response to oxidant-based DNA damage in medulloblastoma cells","volume":"24","year":"2019","journal-title":"Redox Biol"},{"key":"2023111621001275000_2023.11.14.567076v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/nature10334"},{"key":"2023111621001275000_2023.11.14.567076v1.20","doi-asserted-by":"crossref","unstructured":"Stratton, MS , Haldar, SM and McKinsey, TA , 2017. 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