Department of Medical Cosmetology, Dermatology Hospital of Southern Medical University, Guangzhou, China.
Photodermatol Photoimmunol Photomed. 2023 May;39(3):235-245. doi: 10.1111/phpp.12827. Epub 2022 Aug 23.
Mesenchymal stem cells-derived exosome (MSCs-exo) was identified to reduce photoaging. The purpose of this study was to investigate the potential role of microRNA (miR)-29b-3p derived from bone marrow MSCs-exo (BMSCs-exo) in photoaging.
Exosomes were isolated from BMSCs and verified by Western blot. A photoaging cell model was constructed by UVB irradiation of human dermal fibroblasts (HDFs). Quantitative real-time PCR (RT-qPCR) was performed to detect the mRNA levels of miR-29b-3p, collagen type I and matrix metalloproteinases (MMPs). CCK-8, Transwell and flow cytometry were applicated to examine cell viability, migration and apoptosis. Commercial kits are used to measure levels of oxidative stress indicators. Finally, a dual-luciferase reporter assay was applied to validate the target of miR-29b-3p.
Extracted exosomes were positive for HSP70 and CD9. Survival of HDFs increased in an exosome concentration-dependent manner. UVB irradiation inhibited miR-29b-3p levels compared with controls, but BMSCs-exo treatment restored miR-29b-3p levels (p < .05). Additionally, BMSCs-exo-miR-29b-3p reversed the inhibition of HDFs migration and oxidative stress by UVB irradiation, as well as the promotion of apoptosis. However, this reversal was attenuated by the suppression of miR-29b-3p (p < .05). Furthermore, BMSCs-exo-miR-29b-3p also inhibited the degradation of collagen type I and the production of MMPs in photoaging, and they were also eliminated by the reduced miR-29b-3p. Finally, MMP-2 was the target gene of miR-29b-3p.
Our study presented a novel role for BMSCs-exo-miR-29b-3p in improving skin photoaging function, and these findings may provide new insights into the targeted treatment of skin photoaging.
间充质干细胞衍生的外泌体(MSCs-exo)被鉴定为可减少光老化。本研究旨在探讨骨髓间充质干细胞衍生外泌体(BMSCs-exo)中的 microRNA(miR)-29b-3p 在光老化中的潜在作用。
从 BMSCs 中分离外泌体,并通过 Western blot 进行验证。用人真皮成纤维细胞(HDFs)经 UVB 照射构建光老化细胞模型。通过定量实时 PCR(RT-qPCR)检测 miR-29b-3p、I 型胶原和基质金属蛋白酶(MMPs)的 mRNA 水平。应用 CCK-8、Transwell 和流式细胞术检测细胞活力、迁移和凋亡。使用商业试剂盒测量氧化应激指标水平。最后,应用双荧光素酶报告实验验证 miR-29b-3p 的靶基因。
提取的外泌体呈 HSP70 和 CD9 阳性。HDFs 的存活率呈外泌体浓度依赖性增加。与对照组相比,UVB 照射抑制了 miR-29b-3p 的水平,但 BMSCs-exo 处理恢复了 miR-29b-3p 的水平(p<.05)。此外,BMSCs-exo-miR-29b-3p 逆转了 UVB 照射对 HDFs 迁移和氧化应激的抑制作用,以及对凋亡的促进作用。然而,抑制 miR-29b-3p 减弱了这种逆转作用(p<.05)。此外,BMSCs-exo-miR-29b-3p 还抑制了光老化中 I 型胶原的降解和 MMPs 的产生,而 miR-29b-3p 的减少消除了这些作用。最后,MMP-2 是 miR-29b-3p 的靶基因。
本研究提出了 BMSCs-exo-miR-29b-3p 在改善皮肤光老化功能方面的新作用,这些发现可能为皮肤光老化的靶向治疗提供新的思路。