Ye Shasha, Lin Jingjing, Zhang Yujie, Li Jiana, Wang Yichen, Liang Fei, Wu Junyi, Xu Yifan, Lin Li, Zhao Yeli
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Pharmacy department, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, Zhejiang, China.
Biochim Biophys Acta Mol Basis Dis. 2025 Apr;1871(4):167724. doi: 10.1016/j.bbadis.2025.167724. Epub 2025 Feb 27.
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.
UVB irradiation (270 mJ/cm) 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.
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.
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.
紫外线B（UVB）照射会损伤皮肤组织。糖尿病会加重皮肤损伤。成纤维细胞生长因子21（FGF21）在发挥保护作用和促进组织修复方面具有重要作用。因此，本研究旨在探讨重组人FGF21（rhFGF21）对受UVB损伤的糖尿病皮肤的影响。
对糖尿病小鼠连续5天进行UVB照射（270 mJ/cm）以建立UVB照射的皮肤损伤模型，照射后每天给予rhFGF21。将人永生化角质形成细胞（HaCaT）和小鼠腹腔巨噬细胞（MPM）在高糖（HG）条件下培养3天，然后在UVB照射或脂多糖（LPS）刺激前用rhFGF21处理1小时。我们通过激光多普勒血流仪、组织病理学染色、TUNEL检测、RT-PCR、蛋白质印迹、MTT检测和Hoechst 33258染色分析UVB照射对糖尿病皮肤的影响。
我们的研究结果表明，糖尿病小鼠的皮肤受到UVB照射的损伤更严重，而rhFGF21减轻了这种损伤。RhFGF21抑制了糖尿病小鼠皮肤组织中的细胞凋亡和炎症反应。这些变化主要表现为小鼠表皮细胞和腹腔巨噬细胞中沉默调节蛋白1（SIRT1）水平的升高。此外，rhFGF21不仅提高了HaCaT细胞的存活率，还降低了MPM中促炎细胞因子的产生。值得注意的是，SIRT1抑制剂（EX527）能够逆转这些作用。
RhFGF21减轻UVB诱导的糖尿病小鼠皮肤损伤，主要是通过SIRT信号通路抑制表皮细胞凋亡和巨噬细胞介导的炎症反应。
