Genetic lineage tracing defines myofibroblast origin and function in the injured heart
Citations Over TimeTop 1% of 2016 papers
Abstract
Cardiac fibroblasts convert to myofibroblasts with injury to mediate healing after acute myocardial infarction (MI) and to mediate long-standing fibrosis with chronic disease. Myofibroblasts remain a poorly defined cell type in terms of their origins and functional effects in vivo. Here we generate Postn (periostin) gene-targeted mice containing a tamoxifen-inducible Cre for cellular lineage-tracing analysis. This Postn allele identifies essentially all myofibroblasts within the heart and multiple other tissues. Lineage tracing with four additional Cre-expressing mouse lines shows that periostin-expressing myofibroblasts in the heart derive from tissue-resident fibroblasts of the Tcf21 lineage, but not endothelial, immune/myeloid or smooth muscle cells. Deletion of periostin(+) myofibroblasts reduces collagen production and scar formation after MI. Periostin-traced myofibroblasts also revert back to a less-activated state upon injury resolution. Our results define the myofibroblast as a periostin-expressing cell type necessary for adaptive healing and fibrosis in the heart, which arises from Tcf21(+) tissue-resident fibroblasts.
Related Papers
- → The role of periostin in tissue remodeling across health and disease(2013)412 cited
- → Periostin, a Matricellular Protein, Plays a Role in the Induction of Chemokines in Pulmonary Fibrosis(2012)171 cited
- → Periostin, a matricellular protein, accelerates cutaneous wound repair by activating dermal fibroblasts(2012)119 cited
- → Matricellular Protein Periostin Mediates Intestinal Inflammation through the Activation of Nuclear Factor κB Signaling(2016)41 cited
- → Faculty Opinions recommendation of Matricellular protein periostin contributes to hepatic inflammation and fibrosis.(2016)