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

RNA sequencing was performed on uninjured, and injured (FSP1, and aSMA expressing) fibroblasts from mice hearts. Fibrosis accompanying wound healing can drive the failure of many different organs. Activated fibroblasts are the principal determinants of post-injury pathological fibrosis as well as physiological repair, making them a difficult therapeutic target. Fibroblasts are a heterogeneous cell population lacking unique functional classification. We demonstrated that FSP1 and aSMA expressing cells are distinct, post-injury fibroblasts in the heart, kidney, and skin and exhibit unique temporal expression patterns. Using mice that express GFP under the FSP1 or aSMA promoters, we isolated these fibroblasts from mouse hearts after myocardial infarction. Protein and transcript arrays, cellular assays as well as in vivo granulation tissue formation were used to determine their functional role(s) in healing and fibrosis. Whereas aSMA+ fibroblasts predominated in producing matrix proteins, FSP1+ fibroblasts significantly promoted angiogenesis. These studies have the potential to shift our focus towards viewing fibroblasts not only molecularly but also as functionally heterogeneous and provide a new paradigm with which to approach treatment for organ fibrosis. Overall design: Fibroblasts were isolated from uninjured BL6 mice for control. FSP1 and aSMA expressing fibroblasts were isolated from transgenic mice that express GFP under FSP1 or aSMA promoter. GFP positive cells were freshly sorted 10 days following myocardial infarction from mice ventricles. RNA was prepared using Ambion RNAqueous kit and submitted for RNA sequencing.

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Saraswati S, Marrow SMW, Watch LA, Young PP