2026-06-14T03:29:04Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/66762024-10-31T12:01:18Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
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
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Swiss National Science Foundation
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Unión Europea. Comisión Europea
funder
Fundación ProCNIC
2018-11-22T08:10:52Z
2018-11-22T08:10:52Z
2018
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
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.
eng
Heart regeneration
Fibroblast inactivation
Zebrafish
Fibrosis
Cardiomyocyte proliferation
Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart
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