人真皮成纤维细胞来源细胞外囊泡通过miRNA-22-5p-GDF11轴改善皮肤光老化

Abstract

Aging is the leading cause of several degenerative diseases. Photoaging due to ultraviolet (UV) exposure accounts for more than 80% of facial aging, which is a complex and incompletely understood process. Here, we explored the mechanisms of skin photoaging and increased chromatin accessibility in UVB-irradiated human dermal fibroblasts (UVB-HDFs). Especially, we investigated key skin photoaging pathways and inflammatory responses characterized by exons occupied by active and repressive chromatin marks. mRNA sequencing revealed changes in mRNA expression levels—1180 genes were upregulated, and 1080 genes were downregulated in UVB-HDFs. In addition, 393 differentially expressed microRNAs (miRNAs) were detected in the extracellular vesicles (EVs) derived from UVB-HDFs; among these miRNAs, miRNA-22-5p (miR-22-5p) was significantly upregulated and targeted growth differentiation factor 11 (GDF11). We determined that GDF11 expression in human skin tissues was strongly associated with age, and GDF11 overexpression in HDFs attenuated UVB-induced damage. Furthermore, when EVs derived from miR-22-5p-inhibited HDF spheroids were administered to UVB-irradiated nude mice, they ameliorated skin photoaging. These findings suggest that the downregulation of miR-22-5p in EVs of HDFs can regulate GDF11 to treat skin photoaging. Our study provides a potential cell-free approach for promoting skin repair and treating skin photoaging.