Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, Bengbu Medical College, Bengbu, Anhui, China.
Photochem Photobiol. 2023 Nov-Dec;99(6):1456-1467. doi: 10.1111/php.13801. Epub 2023 Mar 20.
UVB-induced photoaging is characterized by wrinkle formation, slackness and senile plaques, affecting the health and beauty of human being. Our previous study revealed that exosomes derived from adipose-derived stem cells (ADSCs) could efficiently alleviate UVB-induced photodamage. However, the functional ingredients in exosomes were undefined. LncRNA H19, one of the well-researched lncRNAs in exosomes, exhibits multiple physiological effects. This study aims to demonstrate the photo-protective role of lncRNA H19 on skin photoaging in UVB-irradiated human skin fibroblasts cells (HSFs) and Kunming mice. LncRNA H19-overexpressing exosomes (H19-Exo) were isolated from the supernatant of ADSCs infected with lncRNA H19-loaded lentivirus. The results showed that H19-Exo significantly inhibited MMPs production, DNA damage and ROS generation while enhancing procollagen type I synthesis in UVB-irradiated HSFs. Meanwhile, H19-Exo markedly reversed epidermal thickening and collagen degradation in UVB-irradiated mice. Furthermore, luciferase reporter assays indicated that lncRNA H19 acted as a sponge for miR-138 expression, and SIRT1 was targeted by miR-138. Evidence from both in vitro and in vivo studies also revealed that H19-Exo could enhance SIRT1 expression by knocking down miR-138. In conclusion, lncRNA H19 served as a therapeutic candidate in treating UVB-induced skin photoaging by upregulation of SIRT1 via miR-138.
UVB 诱导的光老化表现为皱纹形成、松弛和老年斑,影响人类的健康和美丽。我们之前的研究表明,脂肪来源干细胞(ADSCs)来源的外泌体可以有效缓解 UVB 诱导的光损伤。然而,外泌体中的功能成分尚不清楚。LncRNA H19 是外泌体中研究较多的 lncRNA 之一,具有多种生理作用。本研究旨在证明 lncRNA H19 在 UVB 照射的人皮肤成纤维细胞(HSFs)和昆明小鼠皮肤光老化中的光保护作用。从感染了负载 lncRNA H19 的慢病毒的 ADSCs 上清液中分离出 lncRNA H19 过表达的外泌体(H19-Exo)。结果表明,H19-Exo 显著抑制 MMPs 产生、DNA 损伤和 ROS 生成,同时增强 UVB 照射的 HSFs 中 I 型前胶原的合成。同时,H19-Exo 明显逆转了 UVB 照射小鼠的表皮增厚和胶原降解。此外,荧光素酶报告基因实验表明,lncRNA H19 作为 miR-138 表达的海绵,SIRT1 是 miR-138 的靶基因。体外和体内研究的证据也表明,H19-Exo 通过敲低 miR-138 可以增强 SIRT1 的表达。总之,lncRNA H19 通过上调 miR-138 增强 SIRT1 的表达,成为治疗 UVB 诱导皮肤光老化的治疗候选物。