Both SIRT1 and UVA radiation are involved in cellular damage processes such as apoptosis, senescence and ageing. MicroRNAs (miRNAs) have been reported to be closely related to UV radiation, as well as to SIRT1. In this study, we investigated the connections among SIRT1, UVA and miRNA in human skin primary fibroblasts. Our results showed that UVA altered the protein level of SIRT1 in a time point–dependent manner. Using miRNA microarray, bioinformatics analysis, we found that knocking down SIRT1 could cause up‐regulation of miR‐27a‐5p and the latter could down‐regulate SMAD2, and these results were verified by qRT‐PCR or Western blot. Furthermore, UVA radiation (5 J/cm²), knocking down SIRT1 or overexpression of miR‐27a‐5p led to increased expression of MMP1, and decreased expressions of COL1 and BCL2. We also found additive impacts on MMP1, COL1 and BCL2 under the combination of UVA radiation + Sirtinol (SIRT1 inhibitor), or UVA radiation + miR‐27a‐5p mimic. SIRT1 activator resveratrol could reverse damage changes caused by UVA radiation. Besides, absent of SIRT1 or overexpression of miR‐27a‐5p increased cell apoptosis and induced cell arrest in G2/M phase. Taken together, these results demonstrated that UVA could influence a novel SIRT1‐miR‐27a‐5p‐SMAD2‐MMP1/COL1/BCL2 axis in skin primary fibroblasts, and may provide potential therapeutic targets for UVA‐induced skin damage.

中文翻译：

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UVA 影响人皮肤原代成纤维细胞中的 SIRT1-miR-27a-5p-SMAD2-MMP1/COL1/BCL2 轴。

SIRT1 和 UVA 辐射都参与细胞损伤过程，例如细胞凋亡、衰老和衰老。据报道，MicroRNAs (miRNAs) 与紫外线辐射以及 SIRT1 密切相关。在这项研究中，我们研究了人类皮肤原代成纤维细胞中 SIRT1、UVA 和 miRNA 之间的联系。我们的结果表明，UVA 以时间点依赖性方式改变了 SIRT1 的蛋白质水平。使用 miRNA 芯片、生物信息学分析，我们发现敲除 SIRT1 可导致 miR-27a-5p 上调，后者可下调 SMAD2，这些结果通过 qRT-PCR 或蛋白质印迹得到验证。此外，UVA 辐射（5 J/cm ²)，敲除 SIRT1 或过表达 miR-27a-5p 导致 MMP1 表达增加，COL1 和 BCL2 表达减少。我们还发现了在 UVA 辐射 + Sirtinol（SIRT1 抑制剂）或 UVA 辐射 + miR-27a-5p 模拟物的组合下对 MMP1、COL1 和 BCL2 的附加影响。SIRT1 激活剂白藜芦醇可以逆转由 UVA 辐射引起的损伤变化。此外，缺乏 SIRT1 或过表达 miR-27a-5p 会增加细胞凋亡并诱导 G2/M 期细胞停滞。总之，这些结果表明，UVA 可以影响皮肤原代成纤维细胞中新的 SIRT1-miR-27a-5p-SMAD2-MMP1/COL1/BCL2 轴，并可能为 UVA 诱导的皮肤损伤提供潜在的治疗靶点。