Identification of a pro-angiogenic functional role for FSP1-positive fibroblast subtype in wound healing

Autor: Pampee P. Young, Lester A. Watch, Stephanie M. W. Marrow, Sarika Saraswati
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Cellular differentiation
Myocardial Infarction
General Physics and Astronomy
02 engineering and technology
Mice
Fibrosis
lcsh:Science
Bone Marrow Transplantation
Multidisciplinary
Granulation tissue
Cell Differentiation
021001 nanoscience & nanotechnology
medicine.anatomical_structure
cardiovascular system
0210 nano-technology
Myofibroblast
Science
Green Fluorescent Proteins
Neovascularization
Physiologic
Mice
Transgenic
Biology
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
In vivo
medicine
Human Umbilical Vein Endothelial Cells
Animals
Humans
S100 Calcium-Binding Protein A4
Progenitor cell
Fibroblast
Transplantation Chimera
Wound Healing
Myocardium
Calcium-Binding Proteins
General Chemistry
Fibroblasts
medicine.disease
Actins
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Cancer research
lcsh:Q
Angiogenesis
Wound healing
Zdroj: Nature Communications, Vol 10, Iss 1, Pp 1-16 (2019)
Nature Communications
ISSN: 2041-1723
Popis: Fibrosis accompanying wound healing can drive the failure of many different organs. Activated fibroblasts are the principal determinants of post-injury pathological fibrosis along with physiological repair, making them a difficult therapeutic target. Although activated fibroblasts are phenotypically heterogeneous, they are not recognized as distinct functional entities. Using mice that express GFP under the FSP1 or αSMA promoter, we characterized two non-overlapping fibroblast subtypes from mouse hearts after myocardial infarction. Here, we report the identification of FSP1-GFP+ cells as a non-pericyte, non-hematopoietic fibroblast subpopulation with a predominant pro-angiogenic role, characterized by in vitro phenotypic/cellular/ultrastructural studies and in vivo granulation tissue formation assays combined with transcriptomics and proteomics. This work identifies a fibroblast subtype that is functionally distinct from the pro-fibrotic αSMA-expressing myofibroblast subtype. Our study has the potential to shift our focus towards viewing fibroblasts as molecularly and functionally heterogeneous and provides a paradigm to approach treatment for organ fibrosis.
Activated fibroblasts are key contributors to tissue repair after cardiac injury. Here, Saraswati et al. identify and characterize a subpopulation of FSP1-positive cardiac fibroblasts with proangiogenic properties in infarcted hearts.
Databáze: OpenAIRE
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