Skin wound healing in different aged Xenopus laevis

Abstract

Xenopus froglets can perfectly heal skin wounds without scarring. To explore whether this capacity is maintained as development proceeds, we examined the cellular responses during the repair of skin injury in 8- and 15-month-old Xenopus laevis. The morphology and sequence of healing phases (i.e., inflammation, new tissue formation, and remodeling) were independent of age, while the timing was delayed in older frogs. At the beginning of postinjury, wound re-epithelialization occurred in form of a thin epithelium followed by a multilayered epidermis containing cells with apoptotic patterns and keratinocytes stained by anti-inducible nitric oxide synthase (iNOS) antibody. The inflammatory response, early activated by recruitment of blood cells immunoreactive to anti-tumor necrosis factor (TNF)-α, iNOS, transforming growth factor (TGF)-β1, and matrix metalloproteinase (MMP)-9, persisted over time. The dermis repaired by a granulation tissue with extensive angiogenesis, inflammatory cells, fibroblasts, and anti-α-SMA positive myofibroblasts. As the healing progressed, wounded areas displayed vascular regression, decrease in cellularity, and rearrangement of provisional matrix. The epidermis restored to a prewound morphology while granulation tissue was replaced by a fibrous tissue in a scar-like pattern. The quantitative PCR analysis demonstrated an up-regulated expression of Xenopus suppressor of cytokine signaling 3 (XSOCS-3) and Xenopus transforming growth factor-β2 (XTGF-β2) soon after wounding and peak levels were detected when granulation tissue was well developed with a large number of inflammatory cells. The findings indicate that X. laevis skin wound healing occurred by a combination of regeneration (in epidermis) and repair (in dermis) and, in contrast to froglet scarless wound healing, the growth to a more mature adult stage is associated with a decrease in regenerative capacity with scar-like tissue formation.

Scar‐free cutaneous wound healing in the leopard gecko, Eublepharis macularius

“…; Bertolotti et al. ). Whereas the mosaic pavement of imbricating scales is regenerated following wounding in leopard geckos, the conical‐shaped tubercle scales are not.…”

“…; Bertolotti et al. ). Among various mammalian species, including mice and humans, the foetus is capable of scar‐free cutaneous wound healing until early‐ to mid‐gestation (Lorenz et al.…”

The cytokines of pulmonary fibrosis: Much learned, much more to learn

“…That immune and inflammatory mechanisms are the master regulators of tissue repair and fibrosis is suggested by studies in which lower vertebrates utilize scarless repair and regeneration or, alternatively, fibrosis, depending on immune and inflammatory cell engagement [59][60][61][62][63]. Finally, wide-ranging research over the past few decades into possible immune and inflammatory causes of fibrosis has led to identification of several major functional families of molecules that are undoubtedly pro-or antifibrotic.…”

Learning from regeneration research organisms: The circuitous road to scar free wound healing

“…A benefit to using Xenopus as a model is that they are able to regenerate skin appendages, such as exocrine glands. Additionally, Xenopus have a multi-layered epidermis, similar to that of mammals (Bertolotti et al, 2013; Caddy et al, 2010; Franchini and Bertolotti, 2014; Franchini et al, 2016; Otsuka-Yamaguchi et al, 2017; Yoshii et al, 2005). Just like frogs, urodele amphibians, such as newts and axolotls, also have the ability to regenerate skin appendages scar-free (Fig.…”