Tissue Repair Laboratory, Rio de Janeiro State University, Rio de Janeiro, Rio de Janeiro, Brazil.
Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, IL, USA.
FASEB J. 2021 Apr;35(4):e21443. doi: 10.1096/fj.202002078R.
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 α β 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.
细胞凋亡的有效清除是伤口愈合过程中至关重要的一步。特别是，在伤口愈合过程中血管的退化会产生大量凋亡的内皮细胞（ApoEC），这些细胞必须被清除。在考虑 ApoEC 的命运和伤口愈合过程中纤维母细胞的存在时，我们假设纤维母细胞可能作为参与内皮细胞清除的吞噬细胞。本研究探讨了真皮纤维母细胞是否吞噬 ApoEC，这种摄取是否改变了真皮纤维母细胞的表型，以及涉及到的生物学分子。在体内和体外研究中，ApoEC 被吞噬后，纤维母细胞获得了促愈合表型（细胞迁移、收缩、α-平滑肌肌动蛋白表达和胶原蛋白沉积增加）。此外，纤维母细胞摄取 ApoEC 部分是通过乳脂肪球-EGF 因子 8 蛋白/整合素αβ途径介导的。我们的研究表明纤维母细胞在清除 ApoEC 方面具有新的功能，并表明这种能力对组织修复和纤维化具有重要意义。
