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Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair.
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.
Afiliación
  • Simões FC; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.
  • Cahill TJ; Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
  • Kenyon A; BHF Oxbridge Centre of Regenerative Medicine, University of Oxford, Oxford, UK.
  • Gavriouchkina D; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.
  • Vieira JM; BHF Oxbridge Centre of Regenerative Medicine, University of Oxford, Oxford, UK.
  • Sun X; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Pezzolla D; Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
  • Ravaud C; Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
  • Masmanian E; Molecular Genetics Unit, Okinawa Institute of Science & Technology, 1919-1 Tancha, Onna, 904-0495, Japan.
  • Weinberger M; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.
  • Mayes S; BHF Oxbridge Centre of Regenerative Medicine, University of Oxford, Oxford, UK.
  • Lemieux ME; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.
  • Barnette DN; BHF Oxbridge Centre of Regenerative Medicine, University of Oxford, Oxford, UK.
  • Gunadasa-Rohling M; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Williams RM; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.
  • Greaves DR; BHF Oxbridge Centre of Regenerative Medicine, University of Oxford, Oxford, UK.
  • Trinh LA; Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
  • Fraser SE; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.
  • Dallas SL; Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
  • Choudhury RP; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.
  • Sauka-Spengler T; Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
  • Riley PR; Bioinfo, Plantagenet, Canada.
Nat Commun ; 11(1): 600, 2020 01 30.
Article en En | MEDLINE | ID: mdl-32001677
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 GFPtpz-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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cicatrización de Heridas / Pez Cebra / Colágeno / Cicatriz / Corazón / Macrófagos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cicatrización de Heridas / Pez Cebra / Colágeno / Cicatriz / Corazón / Macrófagos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido