Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair

Canonical roles for macrophages in mediating the fibrotic response after a heart attack include extracellular matrix turnover and activation of cardiac fibroblasts to initiate collagen deposition. Here we reveal that macrophages directly contribute collagen to the forming post-injury scar. Unbiased...

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Vydáno v:	Nature communications Ročník 11; číslo 1; s. 600 - 17
Hlavní autoři:	Simões, Filipa C., Cahill, Thomas J., Kenyon, Amy, Gavriouchkina, Daria, Vieira, Joaquim M., Sun, Xin, Pezzolla, Daniela, Ravaud, Christophe, Masmanian, Eva, Weinberger, Michael, Mayes, Sarah, Lemieux, Madeleine E., Barnette, Damien N., Gunadasa-Rohling, Mala, Williams, Ruth M., Greaves, David R., Trinh, Le A., Fraser, Scott E., Dallas, Sarah L., Choudhury, Robin P., Sauka-Spengler, Tatjana, Riley, Paul R.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 30.01.2020 Nature Publishing Group Nature Portfolio
Témata:	13/1 13/106 13/31 13/51 38/32 38/39 38/91 631/250/2504 64/110 64/116 692/4019/592/2725 Adoptive Transfer Animals Cell activation Cicatrix - metabolism Cicatrix - pathology Collagen Collagen - metabolism Danio rerio Deposition Embryo, Mammalian - metabolism Extracellular matrix Extracellular Matrix Proteins - metabolism Fibroblasts Fibrosis Gene Expression Regulation Green Fluorescent Proteins - metabolism Heart Heart - physiopathology Heart attacks Humanities and Social Sciences Injuries Macrophages Macrophages - metabolism Macrophages - pathology Mice Monocytes - metabolism multidisciplinary Myocardial infarction Regeneration RNA, Messenger - genetics RNA, Messenger - metabolism Scars Science Science (multidisciplinary) Spleen - pathology Transcription, Genetic Transcriptome - genetics Wound Healing Zebrafish Zebrafish - embryology Zebrafish - physiology Zebrafish Proteins - metabolism
ISSN:	2041-1723, 2041-1723
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Shrnutí:	Canonical roles for macrophages in mediating the fibrotic response after a heart attack include extracellular matrix turnover and activation of cardiac fibroblasts to initiate collagen deposition. Here we reveal that macrophages directly contribute collagen to the forming post-injury scar. Unbiased transcriptomics shows an upregulation of collagens in both zebrafish and mouse macrophages following heart injury. Adoptive transfer of macrophages, from either collagen-tagged zebrafish or adult mouse GFP tpz -collagen donors, enhances scar formation via cell autonomous production of collagen. In zebrafish, the majority of tagged collagen localises proximal to the injury, within the overlying epicardial region, suggesting a possible distinction between macrophage-deposited collagen and that predominantly laid-down by myofibroblasts. Macrophage-specific targeting of col4a3bpa and cognate col4a1 in zebrafish significantly reduces scarring in cryoinjured hosts. Our findings contrast with the current model of scarring, whereby collagen deposition is exclusively attributed to myofibroblasts, and implicate macrophages as direct contributors to fibrosis during heart repair. Macrophages mediate the fibrotic response after a heart attack by extracellular matrix turnover and cardiac fibroblasts activation. Here the authors identify an evolutionarily-conserved function of macrophages that contributes directly to the forming post-injury scar through cell-autonomous deposition of collagen.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-019-14263-2