{"id":57526,"date":"2026-03-04T22:18:04","date_gmt":"2026-03-04T21:18:04","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/03\/04\/the-cnc-bzip-transcription-factor-nrf2-controls-expression-of-matrix-metalloproteases-in-murine-macrophagesabel-d-ang-on-4-de-march-de-2026-at-1100\/"},"modified":"2026-03-04T22:18:04","modified_gmt":"2026-03-04T21:18:04","slug":"the-cnc-bzip-transcription-factor-nrf2-controls-expression-of-matrix-metalloproteases-in-murine-macrophagesabel-d-ang-on-4-de-march-de-2026-at-1100","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/03\/04\/the-cnc-bzip-transcription-factor-nrf2-controls-expression-of-matrix-metalloproteases-in-murine-macrophagesabel-d-ang-on-4-de-march-de-2026-at-1100\/","title":{"rendered":"The CNC-bZIP transcription factor Nrf2 controls expression of matrix metalloproteases in murine macrophages\u200bAbel D Ang   on 4 de March de 2026 at 11:00"},"content":{"rendered":"<div>\n<p><b>J Leukoc Biol<\/b>. 2026 Mar 3;118(3):qiag021. doi: 10.1093\/jleuko\/qiag021.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<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.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41778891\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=8405628&amp;ff=20260304161754&amp;v=2.19.0.post6+133c1fe\">41778891<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jleuko\/qiag021\">10.1093\/jleuko\/qiag021<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Leukoc Biol. 2026 Mar 3;118(3):qiag021. doi: 10.1093\/jleuko\/qiag021. ABSTRACT 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 &#8230; <a title=\"The CNC-bZIP transcription factor Nrf2 controls expression of matrix metalloproteases in murine macrophages\u200bAbel D Ang   on 4 de March de 2026 at 11:00\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/03\/04\/the-cnc-bzip-transcription-factor-nrf2-controls-expression-of-matrix-metalloproteases-in-murine-macrophagesabel-d-ang-on-4-de-march-de-2026-at-1100\/\" aria-label=\"Read more about The CNC-bZIP transcription factor Nrf2 controls expression of matrix metalloproteases in murine macrophages\u200bAbel D Ang   on 4 de March de 2026 at 11:00\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[86,42],"tags":[],"class_list":["post-57526","post","type-post","status-publish","format-standard","hentry","category-journal-of-leukocyte-biology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/57526","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=57526"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/57526\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=57526"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=57526"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=57526"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}