RhFGF21 protects the skin from UVB irradiation in diabetic mice through the inhibition of epidermal cell apoptosis and macrophage-mediated inflammation via the SIRT1 signaling pathway.

BACKGROUND

Ultraviolet B (UVB) irradiation can damage skin tissue. Diabetes aggravates skin lesions. Fibroblast growth factor 21 (FGF21) is significantly involved in exerting protective effects and facilitating tissue repair. Therefore, this study aimed to investigate the impact of recombinant human FGF21 (rhFGF21) on diabetic skin affected by UVB damage.

METHODS

UVB irradiation (270 mJ/cm2) was administered to diabetic mice for 5 consecutive days to establish UVB-irradiated skin injury, and rhFGF21 was administered daily after irradiation. Human immortalized keratinocytes (HaCaT) and mouse peritoneal macrophages (MPMs) were cultured under high glucose (HG) conditions for 3 days, followed by treatment with rhFGF21 for 1 h before UVB irradiation or lipopolysaccharide (LPS) stimulation. We analyzed the effects of UVB irradiation on diabetic skin via laser Doppler flowmetry, histopathological staining, TUNEL assays, RT-PCR, Western blotting, MTT assays and Hoechst 33258 staining.

RESULTS

Our findings indicated that the skin of diabetic mice was more severely damaged by UVB irradiation, and rhFGF21 alleviated this damage. RhFGF21 inhibited apoptosis and inflammatory responses in the skin tissues of diabetic mice. These changes were primarily reflected in increase of the sirtuin 1 (SIRT1) level in epidermal cells and peritoneal macrophages of mice. Moreover, rhFGF21 not only increased the survival rate of HaCaT cells but also decreased the generation of pro-inflammatory cytokines in MPMs. Notably, SIRT1 inhibitor (EX527) was capable of reversing these effects.

CONCLUSIONS

RhFGF21 attenuates UVB-induced damage to the skin of diabetic mice, predominantly by suppressing epidermal cell apoptosis and macrophage-mediated inflammatory responses via the SIRT signaling pathway.