{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:38:37Z","timestamp":1789684717751,"version":"4.0.1"},"reference-count":39,"publisher":"American Society for Cell Biology (ASCB)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:p>Transforming growth factor-\u03b2 (TGF-\u03b2) is an inducer of type I collagen, and uncontrolled collagen production leads to tissue scarring and organ failure. Here we hypothesize that uncovering a molecular mechanism that enables us to switch off type I collagen may prove beneficial in treating fibrosis. For the first time, to our knowledge, we provide evidence that CUX1 acts as a negative regulator of TGF-\u03b2 and potent inhibitor of type I collagen transcription. We show that CUX1, a CCAAT displacement protein, is associated with reduced expression of type I collagen both in vivo and in vitro. We show that enhancing the expression of CUX1 results in effective suppression of type I collagen. We demonstrate that the mechanism by which CUX1 suppresses type I collagen is through interfering with gene transcription. In addition, using an in vivo murine model of aristolochic acid (AA)-induced interstitial fibrosis and human AA nephropathy, we observe that CUX1 expression was significantly reduced in fibrotic tissue when compared to control samples. Moreover, silencing of CUX1 in fibroblasts from kidneys of patients with renal fibrosis resulted in increased type I collagen expression. Furthermore, the abnormal CUX1 expression was restored by addition of TGF-\u03b2 via the p38 mitogen-activated protein kinase pathway. Collectively, our study demonstrates that modifications of CUX1 expression lead to aberrant expression of type I collagen, which may provide a molecular basis for fibrogenesis.<\/jats:p>","DOI":"10.1091\/mbc.e10-08-0669","type":"journal-article","created":{"date-parts":[[2011,4,7]],"date-time":"2011-04-07T04:39:11Z","timestamp":1302151151000},"page":"1836-1844","source":"Crossref","is-referenced-by-count":37,"title":["High doses of TGF-\u03b2 potently suppress type I collagen via the transcription factor<i>CUX1<\/i>"],"prefix":"10.1091","volume":"22","author":[{"given":"Maria","family":"Fragiadaki","sequence":"first","affiliation":[{"name":"Renal Medicine, Imperial College London, Hammersmith Campus, London W12 ONN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsurou","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Renal Medicine, Imperial College London, Hammersmith Campus, London W12 ONN, United 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