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

Saraswati S, Marrow SMW, Watch LA, Young PP
Nat Commun. 2019 10 (1): 3027

PMID: 31289275 · PMCID: PMC6617456 · DOI:10.1038/s41467-019-10965-9

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.

MeSH Terms (20)

Actins Animals Bone Marrow Transplantation Calcium-Binding Proteins Cell Differentiation Disease Models, Animal Fibroblasts Fibrosis Green Fluorescent Proteins Humans Human Umbilical Vein Endothelial Cells Mice Mice, Inbred C57BL Mice, Transgenic Myocardial Infarction Myocardium Neovascularization, Physiologic S100 Calcium-Binding Protein A4 Transplantation Chimera Wound Healing

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