| First Author | Fu X | Year | 2018 |
| Journal | J Clin Invest | Volume | 128 |
| Issue | 5 | Pages | 2127-2143 |
| PubMed ID | 29664017 | Mgi Jnum | J:262811 |
| Mgi Id | MGI:6158810 | Doi | 10.1172/JCI98215 |
| Citation | Fu X, et al. (2018) Specialized fibroblast differentiated states underlie scar formation in the infarcted mouse heart. J Clin Invest 128(5):2127-2143 |
| abstractText | Fibroblasts are a dynamic cell type that achieve selective differentiated states to mediate acute wound healing and long-term tissue remodeling with scarring. With myocardial infarction injury, cardiomyocytes are replaced by secreted extracellular matrix proteins produced by proliferating and differentiating fibroblasts. Here, we employed 3 different mouse lineage-tracing models and stage-specific gene profiling to phenotypically analyze and classify resident cardiac fibroblast dynamics during myocardial infarction injury and stable scar formation. Fibroblasts were activated and highly proliferative, reaching a maximum rate within 2 to 4 days after infarction injury, at which point they expanded 3.5-fold and were maintained long term. By 3 to 7 days, these cells differentiated into myofibroblasts that secreted abundant extracellular matrix proteins and expressed smooth muscle alpha-actin to structurally support the necrotic area. By 7 to 10 days, myofibroblasts lost proliferative ability and smooth muscle alpha-actin expression as the collagen-containing extracellular matrix and scar fully matured. However, these same lineage-traced initial fibroblasts persisted within the scar, achieving a new molecular and stable differentiated state referred to as a matrifibrocyte, which was also observed in the scars of human hearts. These cells express common and unique extracellular matrix and tendon genes that are more specialized to support the mature scar. |
