College of Life Sciences, Liaoning Normal University, Dalian 116081, China.
Lamprey Research Center, Liaoning Normal University, Dalian 116081, China.
Int J Mol Sci. 2023 Feb 6;24(4):3213. doi: 10.3390/ijms24043213.
Skin is a natural barrier between the body and the external environment, and this important multifunctional organ plays roles in body temperature regulation, sensory stimulation, mucus secretion, metabolite excretion and immune defense. Lampreys, as ancient vertebrates, rarely experience infection of damaged skin during farming and efficiently promote skin wound healing. However, the mechanism underlying these wound healing and regenerative effects is unclear. Our histology and transcriptomics results demonstrate that lampreys regenerate a nearly complete skin structure in damaged epidermis, including the secretory glands, and will almost not be infected, even if experiencing full-thickness damage. In addition, , and participate in the lipolysis process to provide space for infiltrating cells. A large number of red blood cells migrate to the site of injury and exert proinflammatory effects, upregulating the expression of proinflammatory factors such as - and -. Based on a lamprey skin damage healing model, adipocytes and red blood cells in the subcutaneous fat layer can promote wound healing, which provides a new approach for the study of skin healing mechanisms. Transcriptome data reveal that mechanical signal transduction pathways are mainly regulated by focal adhesion kinase and that the actin cytoskeleton plays an important role in the healing of lamprey skin injuries. We identified RAC1 as a key regulatory gene that is necessary and partially sufficient for wound regeneration. Insights into the mechanisms of lamprey skin injury and healing will provide a theoretical basis for overcoming the challenges associated with chronic healing and scar healing in the clinic.
皮肤是机体与外界环境之间的天然屏障,作为一种重要的多功能器官,皮肤在体温调节、感觉刺激、黏液分泌、代谢物排泄和免疫防御中发挥作用。七鳃鳗作为古老的脊椎动物,在养殖过程中很少经历受损皮肤的感染,并且能够有效地促进皮肤伤口愈合。然而,这些伤口愈合和再生作用的机制尚不清楚。我们的组织学和转录组学结果表明,七鳃鳗在受损的表皮中再生出几乎完整的皮肤结构,包括分泌腺,而且几乎不会受到感染,即使是全层损伤。此外, 、 和 参与脂肪分解过程,为浸润细胞提供空间。大量的红细胞迁移到损伤部位,发挥促炎作用,上调促炎因子如 - 和 - 的表达。基于七鳃鳗皮肤损伤愈合模型,皮下脂肪层中的脂肪细胞和红细胞可以促进伤口愈合,这为皮肤愈合机制的研究提供了新的途径。转录组数据显示,机械信号转导途径主要受粘着斑激酶调节,细胞骨架肌动蛋白在七鳃鳗皮肤损伤愈合中起重要作用。我们鉴定出 RAC1 是一个关键调节基因,它对伤口再生是必要的和部分充分的。对七鳃鳗皮肤损伤和愈合机制的深入了解将为克服临床慢性愈合和瘢痕愈合所面临的挑战提供理论依据。