2026-06-14T03:30:24Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/66762024-10-31T12:01:18Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Sanchez-Iranzo, Hector author Galardi-Castilla, Maria author Sanz-Morejon, Andres author Gonzalez-Rosa, Juan Manuel author Costa, Ricardo author Ernst, Alexander author Sainz de Aja, Julio author Langa, Xavier author Mercader, Nadia author 2018 In the zebrafish (Danio rerio), regeneration and fibrosis after cardiac injury are not mutually exclusive responses. Upon cardiac cryoinjury, collagen and other extracellular matrix (ECM) proteins accumulate at the injury site. However, in contrast to the situation in mammals, fibrosis is transient in zebrafish and its regression is concomitant with regrowth of the myocardial wall. Little is known about the cells producing this fibrotic tissue or how it resolves. Using novel genetic tools to mark periostin b- and collagen 1alpha2 (col1a2)-expressing cells in combination with transcriptome analysis, we explored the sources of activated fibroblasts and traced their fate. We describe that during fibrosis regression, fibroblasts are not fully eliminated but become inactivated. Unexpectedly, limiting the fibrotic response by genetic ablation of col1a2-expressing cells impaired cardiomyocyte proliferation. We conclude that ECMproducing cells are key players in the regenerative process and suggest that antifibrotic therapies might be less efficient than strategies targeting fibroblast inactivation. Proc Natl Acad Sci U S A. 2018; 115(16):4188-93 10.1073/pnas.1716713115 0027-8424 Proceedings of the National Academy of Sciences 29610343 http://hdl.handle.net/20.500.12105/6676 Heart regeneration Fibroblast inactivation Zebrafish Fibrosis Cardiomyocyte proliferation Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart