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Identification of a pro-angiogenic functional role for FSP1-positive fibroblast
subtype in wound healing.
Authors Saraswati S, Marrow SMW, Watch LA, Young PP
Submitted By Submitted Externally on 8/6/2019
Status Published
Journal Nature communications
Year 2019
Date Published 7/1/2019
Volume : Pages 10 : 3027
PubMed Reference 31289275
Abstract 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 aSMA 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 aSMA-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.


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