Center for Wound Healing and Tissue Regeneration, University of Illinois Chicago, Chicago, IL, USA.
Department of Microbiology and Immunology, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.
Sci Rep. 2023 May 30;13(1):8728. doi: 10.1038/s41598-023-35558-x.
Many factors regulate scar formation, which yields a modified extracellular matrix (ECM). Among ECM components, microfibril-associated proteins have been minimally explored in the context of skin wound repair. Microfibril-associated protein 5 (MFAP5), a small 25 kD serine and threonine rich microfibril-associated protein, influences microfibril function and modulates major extracellular signaling pathways. Though known to be associated with fibrosis and angiogenesis in certain pathologies, MFAP5's role in wound healing is unknown. Using a murine model of skin wound repair, we found that MFAP5 is significantly expressed during the proliferative and remodeling phases of healing. Analysis of existing single-cell RNA-sequencing data from mouse skin wounds identified two fibroblast subpopulations as the main expressors of MFAP5 during wound healing. Furthermore, neutralization of MFAP5 in healing mouse wounds decreased collagen deposition and refined angiogenesis without altering wound closure. In vitro, recombinant MFAP5 significantly enhanced dermal fibroblast migration, collagen contractility, and expression of pro-fibrotic genes. Additionally, TGF-ß1 increased MFAP5 expression and production in dermal fibroblasts. Our findings suggest that MFAP5 regulates fibroblast function and influences scar formation in healing wounds. Our work demonstrates a previously undescribed role for MFAP5 and suggests that microfibril-associated proteins may be significant modulators of wound healing outcomes and scarring.
许多因素调节瘢痕形成，导致细胞外基质（ECM）的改变。在 ECM 成分中，微纤维相关蛋白在皮肤伤口修复方面的研究很少。微纤维相关蛋白 5（MFAP5）是一种 25kD 的富含丝氨酸和苏氨酸的小微纤维相关蛋白，它影响微纤维的功能并调节主要的细胞外信号通路。尽管已知在某些病理情况下与纤维化和血管生成有关，但 MFAP5 在伤口愈合中的作用尚不清楚。我们使用皮肤伤口修复的小鼠模型发现，MFAP5 在愈合的增殖和重塑阶段显著表达。对来自小鼠皮肤伤口的现有单细胞 RNA 测序数据的分析确定了两个成纤维细胞亚群是 MFAP5 在伤口愈合过程中的主要表达者。此外，在愈合的小鼠伤口中中和 MFAP5 减少了胶原蛋白沉积和精细的血管生成，而不改变伤口闭合。在体外，重组 MFAP5 显著增强了真皮成纤维细胞的迁移、胶原蛋白收缩性和促纤维化基因的表达。此外，TGF-β1 增加了真皮成纤维细胞中 MFAP5 的表达和产生。我们的研究结果表明，MFAP5 调节成纤维细胞功能并影响愈合伤口中的瘢痕形成。我们的工作表明了 MFAP5 的一个以前未描述的作用，并表明微纤维相关蛋白可能是伤口愈合结局和瘢痕形成的重要调节剂。
