{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:10:55Z","timestamp":1773879055898,"version":"3.50.1"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Liver fibrosis is a chronic condition that often leads to organ failure. Currently, no effective treatment exists for advanced liver fibrosis. De-repression of the transcription factor Nrf2, by inhibition of the ubiquitin ligase substrate adaptor Keap1, is a promising strategy to treat liver fibrosis because Nrf2 augments cytoprotection and blunts the profibrotic TGF-\u03b2 pathway. Herein, Nrf2 is reported to control matrix metalloproteinase (MMP) expression during chronic liver injury, and more specifically in macrophages, which play a key role in the resolution of fibrosis. We found impaired expression of Mmp8, Mmp9, Mmp12, and Mmp14 in the livers of Nrf2-knockout (Nrf2-ko) mice compared to wild-type (WT) mice, both basally and following CCl4 damage. Investigation of bone-marrow-derived macrophages (BMDMs) revealed profoundly impaired expression of Mmp8 and Mmp12 in Nrf2-ko BMDMs and a concomitant hyper-expression in Keap1-knockdown (Keap1-kd) BMDMs, which were corroborated by siRNA knockdown of Nrf2 and macrophage-specific conditional knockout of Nrf2. This trend was observed under basal conditions and post-efferocytosis. Total MMP activity was also found to be highest in the conditioned medium of Keap1-kd post-efferocytosis BMDMs. ChIP-seq revealed Nrf2-binding sites upstream of Mmp12, which also showed the strongest expression response to Nrf2. Lastly, through pharmacological de-repression of Nrf2, using TBE-31 to inhibit Keap1, upregulation of MMP expression was observed in BMDMs and livers of mice following acute liver injury. In conclusion, Nrf2 has been shown to be a regulator of MMP expression and activity in stimulated macrophages, which reveals a new mechanism by which Nrf2 regulates macrophage function.<\/jats:p>","DOI":"10.1093\/jleuko\/qiag021","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T12:39:35Z","timestamp":1771936775000},"source":"Crossref","is-referenced-by-count":0,"title":["The CNC-bZIP transcription factor Nrf2 controls expression of matrix metalloproteases in murine macrophages"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8935-5945","authenticated-orcid":false,"given":"Abel D","family":"Ang","sequence":"first","affiliation":[{"name":"Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee , James Arrott Drive, Dundee DD1 9SY ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharadha","family":"Dayalan Naidu","sequence":"additional","affiliation":[{"name":"Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee , James Arrott Drive, Dundee DD1 9SY ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver J","family":"Read","sequence":"additional","affiliation":[{"name":"Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee , James Arrott Drive, Dundee DD1 9SY ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pingting","family":"Bian","sequence":"additional","affiliation":[{"name":"Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee , James Arrott Drive, Dundee DD1 9SY ,","place":["United 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