Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart.

Sánchez-Iranzo, Héctor; Galardi-Castilla, María; Sanz Morejon, Andrés; González-Rosa, Juan Manuel; Costa, Ricardo; Ernst, Alexander Uwe Johann; Sainz de Aja, Julio; Langa, Xavier; Mercader Huber, Nadia Isabel (2018). Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 115(16), pp. 4188-4193. National Academy of Sciences NAS 10.1073/pnas.1716713115

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In the zebrafish (), 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 - and ()-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 -expressing cells impaired cardiomyocyte proliferation. We conclude that ECM-producing cells are key players in the regenerative process and suggest that antifibrotic therapies might be less efficient than strategies targeting fibroblast inactivation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy
09 Interdisciplinary Units > Microscopy Imaging Center (MIC)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Sanz Morejon, Andrés; Ernst, Alexander Uwe Johann and Mercader Huber, Nadia Isabel

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0027-8424

Publisher:

National Academy of Sciences NAS

Language:

English

Submitter:

Nadia Isabel Mercader Huber

Date Deposited:

03 Jul 2018 07:40

Last Modified:

23 Oct 2019 11:44

Publisher DOI:

10.1073/pnas.1716713115

PubMed ID:

29610343

Uncontrolled Keywords:

cardiomyocyte proliferation fibroblast inactivation fibrosis heart regeneration zebrafish

BORIS DOI:

10.7892/boris.118214

URI:

https://boris.unibe.ch/id/eprint/118214

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