Walker John T, Elliott Christopher G, Forbes Thomas L, Hamilton Douglas W
Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Division of Vascular Surgery, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
J Invest Dermatol. 2016 May;136(5):1042-1050. doi: 10.1016/j.jid.2016.01.014. Epub 2016 Jan 29.
Galectin-3 has been linked to the regulation of several molecular processes essential during acute cutaneous wound healing, but a comprehensive study of the role of galectin-3 has yet to be performed. With known roles in macrophage polarization, myofibroblast differentiation, re-epithelialization, and angiogenesis, we hypothesized that genetic deletion of galectin-3 would significantly impair healing of excisional skin wounds in mice. In wild-type mice, galectin-3 expression correlated temporally with the inflammatory phase of healing. Conversely, genetic deletion of galectin-3 did not alter gross wound healing kinetics even though it resulted in delayed re-epithelialization. Wound composition was not altered up to 15 days after wounding in knockout mice, and isolated dermal fibroblast function in vitro was unchanged. We further explored, spatially, the expression of galectin-3 in human chronic wound tissue in relation to the immune cell infiltrate. We show a decreased mRNA and protein abundance in the wound edge tissue, whereas markers of neutrophils, M1 and M2 macrophages are expressed abundantly. Both transforming growth factor-β1 and tumor necrosis factor-α decrease galectin-3 mRNA abundance in chronic wound edge dermal fibroblasts in vitro, providing a potential mechanism for this decreased expression in chronic wounds.
半乳糖凝集素-3与急性皮肤伤口愈合过程中几个关键的分子过程的调节有关，但对半乳糖凝集素-3作用的全面研究尚未开展。鉴于其在巨噬细胞极化、肌成纤维细胞分化、再上皮化和血管生成中的已知作用，我们推测半乳糖凝集素-3的基因缺失会显著损害小鼠切除性皮肤伤口的愈合。在野生型小鼠中，半乳糖凝集素-3的表达在时间上与愈合的炎症阶段相关。相反，半乳糖凝集素-3的基因缺失并未改变伤口愈合的总体动力学，尽管它导致了再上皮化延迟。在基因敲除小鼠中，受伤后15天内伤口组成未改变，体外分离的真皮成纤维细胞功能也未改变。我们进一步在空间上探究了半乳糖凝集素-3在人类慢性伤口组织中的表达与免疫细胞浸润的关系。我们发现伤口边缘组织中的mRNA和蛋白质丰度降低，而中性粒细胞、M1和M2巨噬细胞的标志物大量表达。体外实验表明，转化生长因子-β1和肿瘤坏死因子-α均会降低慢性伤口边缘真皮成纤维细胞中半乳糖凝集素-3的mRNA丰度，这为慢性伤口中该表达降低提供了一种潜在机制。
