title: Collagen XII Contributes to Epicardial and Connective Tissues in the Zebrafish Heart during Ontogenesis and Regeneration.
abstract: Zebrafish heart regeneration depends on cardiac cell proliferation, epicardium activation and transient reparative tissue deposition. The contribution and the regulation of specific collagen types during the regenerative process, however, remain poorly characterized. Here, we identified that the non-fibrillar type XII collagen, which serves as a matrix-bridging component, is expressed in the epicardium of the zebrafish heart, and is boosted after cryoinjury-induced ventricular damage. During heart regeneration, an intense deposition of Collagen XII covers the outer epicardial cap and the interstitial reparative tissue. Analysis of the activated epicardium and fibroblast markers revealed a heterogeneous cellular origin of Collagen XII. Interestingly, this matrix-bridging collagen co-localized with fibrillar type I collagen and several glycoproteins in the post-injury zone, suggesting its role in tissue cohesion. Using SB431542, a selective inhibitor of the TGF-β receptor, we showed that while the inhibitor treatment did not affect the expression of collagen 12 and collagen 1a2 in the epicardium, it completely suppressed the induction of both genes in the fibrotic tissue. This suggests that distinct mechanisms might regulate collagen expression in the outer heart layer and the inner injury zone. On the basis of this study, we postulate that the TGF-β signaling pathway induces and coordinates formation of a transient collagenous network that comprises fibril-forming Collagen I and fiber-associated Collagen XII, both of which contribute to the reparative matrix of the regenerating zebrafish heart.
authors: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors: Jan
authors: J
authors: Marro
authors: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors: Catherine
authors: C
authors: Pfefferli
authors: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors: Anne-Sophie
authors: AS
authors: de Preux Charles
authors: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors: Thomas
authors: T
authors: Bise
authors: Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors: Anna
authors: http://orcid.org/0000-0003-3881-9284
authors: A
authors: Jaźwińska
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024082:Collagen Type XII / Q000235:genetics / Q000378:metabolism*; D003238:Connective Tissue / Q000378:metabolism*; D004149:Dioxoles / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D017403:In Situ Hybridization; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010496:Pericardium / Q000378:metabolism* / Q000473:pathology; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014746:Vimentin / Q000378:metabolism; D015027:Zebrafish / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D024042:Collagen Type I; D024082:Collagen Type XII; D004149:Dioxoles; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D014746:Vimentin; D029961:Zebrafish Proteins