The study of long-lived and regenerative animal models has revealed diverse protective responses to stressors such as aging and tissue injury. Spiny mice (Acomys) are a unique mammalian model of skin wound regeneration, but their response to other types of physiological skin damage has not been investigated. In this study, we examine how spiny mouse skin responds to acute UVB damage or chronological aging compared to non-regenerative C57Bl/6 mice (M. musculus). We find that, compared to M. musculus, the skin epidermis in A. cahirinus experiences a similar UVB-induced increase in basal cell proliferation but exhibits increased epidermal turnover. Notably, A. cahirinus uniquely form a suprabasal layer co-expressing Keratin 14 and Keratin 10 after UVB exposure concomitant with reduced epidermal inflammatory signaling and reduced markers of DNA damage. In the context of aging, old M. musculus animals exhibit typical hallmarks including epidermal thinning, increased inflammatory signaling and senescence. However, these age-related changes are absent in old A. cahirinus skin. Overall, we find that A. cahirinus have evolved novel responses to skin damage that reveals new aspects of its regenerative phenotype.
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This work was supported by startup funding from the Northeastern University Provost’s Office (to J. D. C.).
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S1 Fig. Acute UVB-exposure induces distinctive pattern of skin epidermal differentiation in A. cahirinus.
A, representative immunofluorescence images of epidermal differentiation markers keratin 14 (K14) and loricrin (Lor) labeling. B, C, D, E individual layer thickness quantification of the (B), K14+/K10– single positive basal layer (C), K14+/K10+ double positive middle suprabasal layer (D), K14–/K10– single positive spinous layer and (E), Lor+ single positive cornified envelope. n = 3 animals per group. Data points are biological replicates and lines indicate group means. *Significantly different (p < 0.05) from the indicated group.
S2 Fig. Attenuated phospho-STAT3Y705 induction after acute UVB-exposure in A. cahirinus.
A, representative immunofluorescence images of epidermal nuclear phosphorylated STAT3 on Y705 (pSTAT3Y705) labeling of skin from control (sham) and UV-irradiated M. musculus and A. cahirinus, collected 24 and 48 hours after exposure. Positive cells are indicated by the pink arrows and the epidermal basement membrane is indicated by the yellow dashed line. Scale bar = 50 μm. B, quantification of pSTAT3Y705 labeling in basal epidermis. n = 3 sham of each species; n = 5 animals at 24hr and 48hr from each species. C, Notch1 and D, Notch2 mRNA expression in whole skin from UV-irradiated M. musculus and A. cahirinus, collected from sham controls or 24 and 48 hours after UVB exposure. For all qPCR: sham, n = 3–4 each species; 24hr n = 5–7 each species; 48hr M. musculus, n = 5–6; 48hr A. cahirinus, n = 3–5 animals per group. All data points are biological replicates and lines indicate group means. *Significantly different (p < 0.05) from the indicated group. †Significant (p < 0.05) overall effect of species.
Wong, Wesley; Kim, Austin; Monaghan, James R.; Seifert, Ashley W.; Maden, Malcolm; and Crane, Justin D., "Spiny Mice (Acomys) Exhibit Attenuated Hallmarks of Aging and Rapid Cell Turnover after UV Exposure in the Skin Epidermis" (2020). Biology Faculty Publications. 199.
S1 Fig. Acute UVB-exposure induces distinctive pattern of skin epidermal differentiation in A. cahirinus. https://doi.org/10.1371/journal.pone.0241617.s001
pone.0241617.s002.tif (5977 kB)
S2 Fig. Attenuated phospho-STAT3Y705 induction after acute UVB-exposure in A. cahirinus. https://doi.org/10.1371/journal.pone.0241617.s002