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This has important consequences such as immune cell infiltration, mainly triggered by the activation of YAP and TAZ proteins. However, other proteins that respond to mechanical modifications remain poorly characterised; in particular, the myocardin\u2010related transcription factors A and B (MRTFs). Here, we referred to these four proteins as mechanical responsive transcriptional cofactors (MRTcoF). We analysed the regulation of MRTcoF proteins in fibrotic livers induced by carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    ) and observed that MRTcoF were differentially regulated during liver fibrosis, predominantly in hepatocytes. Transcriptome analysis suggested that fatty acid and glucose metabolisms, cell proliferation and signalling pathways were regulated by transcriptional enhanced associate domain (TEAD)\u2010 and serum response factor (SRF)\u2010transcriptional programmes in CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010treated livers. Then, we evaluated the protein expression levels of MRTcoF in primary hepatocytes (PH) cultured on tissue culture petri dishes (TCPD). After culture, we observed upregulation of MRTcoF, and downregulation of TAZ after protein increase. Interestingly, despite the increase in MRTFB protein levels, no accumulation of MRTFB was detected in the nucleus. Culture on soft polyacrylamide hydrogels (PAA HGs) attenuated the activation of MRTcoF, having specific implications in the transcriptional regulation of target genes. In contrast, pharmacological inhibition of MRTcoF was not sufficient to halt transcriptional regulation. In summary, a progressive increase of stiffness activates MRTcoF transcriptional complexes in hepatocytes, suggesting a key role of mechano\u2010transduction during liver fibrosis.\n                  <\/jats:p>","DOI":"10.1111\/febs.70570","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T14:09:44Z","timestamp":1777903784000},"page":"6230-6252","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanical stiffness orchestrates distinct regulation of\n                    <scp>MRTFs<\/scp>\n                    and\n                    <scp>YAP<\/scp>\n                    \/\n                    <scp>TAZ<\/scp>\n                    transcriptional cofactors in hepatocytes"],"prefix":"10.1111","volume":"293","author":[{"given":"Brenda Selene","family":"Torres\u2010Ortiz","sequence":"first","affiliation":[{"name":"Facultad de Ciencias Universidad Nacional Aut\u00f3noma de M\u00e9xico 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