Skin wound repair in adult Xenopus laevis

Restoration of tissue integrity and homeostasis after an injury is a fundamental property of all organisms and there is diversity in how this process occurs. The healing response can lead to complete regeneration of tissue structure or repair that involves collagen deposition and scar formation. The regenerative capacity of anuran amphibians depends on the developmental stage and declines as metamorphosis proceeds. Few studies have addressed the ability of adult anurans to heal their wounds: skin repair occurred with scar synthesis in Rana catesbeiana, while it was without scarring in young adult Xenopus froglets. In this work, we investigated the repair of skin wounds in different aged (8 and 15 month old) X. laevis adults to determine the quality of the wound healing response. Molecules (TNF-a, iNOS, MMP-9, a-SMA) and selected genes (SOCS-3, TGF-b2), known to be involved in inflammatory responses and wound healing, were analysed by immunohistochemical reactions and quantitative RT-PCR. The histological results showed similar repair step sequences in different aged frogs: inflammation, new tissue formation and maturation with wound contraction and remodeling. A large infiltrate of neutrophils and macrophages was early seen in the injured area and then lymphocytes were also detected in the granulation tissue. This wound connective tissue was characterized by extensive angiogenesis and transformation of some fibroblasts into anti-a-SMA immunoreactive myofibroblasts which contributed to scar formation. Quantitative RT-PCR analysis demonstrated that the regulator of cytokine signaling, SOCS-3, was rapidly up-regulated after the injury and maintained high levels during the process, while TGF-b2, an important tissue fibrosis promoter, increased when the new tissue was formed and high induced expression persisted later in the repair. The results demonstrated that Xenopus skin regenerative capacity is lost with increasing age of the adult. The outcome of skin wound healing is similar to that of mammals with the formation of a scar-like tissue that may be related to an intense immune response, abundant granulation tissue and wound contraction. Moreover, α-SMA, SOCS-3 and TGFβ promote the tissue repair with expression patterns that seem to be different from those observed in scarless healing.