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The affected cardiac tissue may lose its function permanently. In contrast, zebrafish display a remarkable capacity for scar-free heart regeneration. Previous studies have revealed that syndecan-4 (SDC4) regulates inflammatory response and fibroblast activity following cardiac injury in higher vertebrates. However, whether and how Sdc4 regulates heart regeneration in highly regenerative zebrafish remains unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p>This study showed that <jats:italic>sdc4<\/jats:italic> expression was differentially regulated during zebrafish heart regeneration by transcriptional analysis. Specifically, <jats:italic>sdc4<\/jats:italic> expression increased rapidly and transiently in the early regeneration phase upon ventricular cryoinjury. Moreover, the knockdown of <jats:italic>sdc4<\/jats:italic> led to a significant reduction in extracellular matrix protein deposition, immune cell accumulation, and cell proliferation at the lesion site. The expression of <jats:italic>tgfb1a<\/jats:italic> and <jats:italic>col1a1a<\/jats:italic>, as well as the protein expression of Fibronectin, were all down-regulated under <jats:italic>sdc4<\/jats:italic> knockdown. In addition, we verified that <jats:italic>sdc4<\/jats:italic> expression was required for cardiac repair in zebrafish via in vivo electrocardiogram analysis. Loss of <jats:italic>sdc4<\/jats:italic> expression caused an apparent pathological Q wave and ST elevation, which are signs of human MI patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our findings support that Sdc4 is required to mediate pleiotropic repair responses in the early stage of zebrafish heart regeneration.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11033-024-09531-4","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T04:02:11Z","timestamp":1714708931000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Syndecan-4 is required for early-stage repair responses during zebrafish heart regeneration"],"prefix":"10.1007","volume":"51","author":[{"given":"Zih-Yin","family":"Lai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Chi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Hsun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Chen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Yu","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan-Yun","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiao-Yu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ko-Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Cen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chieh","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence Yu-Min","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Jen","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,3]]},"reference":[{"key":"9531_CR1","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/s41392-022-00925-z","volume":"7","author":"Q Zhang","year":"2022","unstructured":"Zhang Q, Wang L, Wang S, Cheng H, Xu L, Pei G et al (2022) Signaling pathways and targeted therapy for myocardial infarction. 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