Lamprey Wound Healing and Regenerative Effects: The Collaborative Efforts of Diverse Drivers

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, ATGL, DGL and MGL 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 IL-8 and IL-17. 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.