Dermal fibroblast phagocytosis of apoptotic cells: A novel pathway for wound resolution.
Bruna Romana-SouzaLin ChenTrevor R LeonardoZhenlong ChenLuisa A DiPietroPublished in: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2021)
The effective clearance of apoptotic cells is an essential step in the resolution of healing wounds. In particular, blood vessel regression during wound resolution produces a significant number of apoptotic endothelial cells (ApoEC) that must be cleared. In considering the fate of ApoEC and the presence of fibroblasts during wound resolution, we hypothesized that fibroblasts might serve as phagocytes involved in endothelial cell removal. The current study investigated whether dermal fibroblasts engulf ApoEC, whether this uptake alters the phenotype of dermal fibroblasts, and the biological molecules involved. In both in vitro and in vivo studies, following ApoEC engulfment, fibroblasts acquired a pro-healing phenotype (increased cell migration, contractility, α-smooth muscle actin expression, and collagen deposition). In addition, fibroblast uptake of ApoEC was shown to be mediated in part by the milk fat globule-EGF factor 8 protein/integrin αv β5 pathway. Our study demonstrates a novel function of fibroblasts in the clearance of ApoEC and suggests that this capability has significant implications for tissue repair and fibrosis.
Keyphrases
- wound healing
- cell migration
- endothelial cells
- extracellular matrix
- smooth muscle
- cell death
- induced apoptosis
- cell cycle arrest
- anti inflammatory
- single molecule
- adipose tissue
- poor prognosis
- signaling pathway
- endoplasmic reticulum stress
- binding protein
- cell proliferation
- vascular endothelial growth factor
- growth factor
- fatty acid
- amino acid