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By contrast, fibrosis is transient in the injured zebrafish heart, facilitating cell recruitment and providing regenerative cues. The mechanisms that restrain excessive fibrosis while enabling regeneration remain poorly understood. Here we show that fibulin-2 (Fbln2) regulates specific populations of activated epicardial cells to balance the response to cardiac injury. Using genetic tools for Fbln2 dosage, we find that attenuation of epicardial activation stimulates regenerative programs. Mechanistically, we identify epicardial nuclear protein 1b (Nupr1b) as an Fbln2 effector. Using gain- and loss-of-function approaches, we show that Nupr1b controls epicardial myofibroblast abundance. Notably, epicardial-specific overexpression of\n                    <jats:italic>nupr1b<\/jats:italic>\n                    rescued\n                    <jats:italic>fbln2<\/jats:italic>\n                    mutant phenotypes. These findings shed light on how modulation of epicardial cell state transitions through Fbln2\u2013Nupr1b signaling regulates regenerative responses after cardiac injury.\n                  <\/jats:p>","DOI":"10.1038\/s44161-026-00785-8","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T16:01:45Z","timestamp":1772553705000},"page":"218-233","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Attenuation of epicardial activation and myofibroblast abundance via the Fbln2\u2013Nupr1b axis stimulates cardiac regeneration in zebrafish"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2285-6641","authenticated-orcid":false,"given":"G\u00fcls\u00fcm","family":"Kayman K\u00fcrek\u00e7i","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gursimran","family":"Kaur Bajwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoqiu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"Leclerc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"de Chantal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darrell","family":"Belke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Andelfinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin F.","family":"Deniset","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5903-7463","authenticated-orcid":false,"given":"Rub\u00e9n","family":"Mar\u00edn-Juez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"785_CR1","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12872-023-03231-w","volume":"23","author":"N Salari","year":"2023","unstructured":"Salari, N. et al. 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