Long Non‐coding RNA H19‐Overexpressing Exosomes Ameliorate UVB‐Induced Photoaging by Upregulating SIRT1Via Sponging miR‐138

Abstract

AbstractUVB‐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.