NORAD accelerates skin wound healing through extracellular vesicle transfer from hypoxic adipose derived stem cells: miR-524-5p pathway and Pumilio protein mechanism.

Skin wound healing is a multifaceted biological process that encompasses a variety of cell types and intricate signaling pathways. Recent research has uncovered that exosomes derived from adipose stem cells, commonly referred to as ADSC exosomes, play a crucial role in facilitating the healing process. Moreover, it has been demonstrated that an anoxic, or low-oxygen, environment significantly enhances the effectiveness of these exosomes in promoting skin repair. The primary objective of this study was to investigate the underlying mechanisms through which ADSC exosomes contribute to Skin wound healing, particularly by regulating the long non-coding RNA known as NORAD under hypoxic conditions. A significant focus of our research was to examine the interplay between the microRNA miR-524-5p and the Pumilio protein, as we aimed to understand how these molecular interactions might influence the overall healing process. In this study, ADSC exosomes were extracted by simulating hypoxia in vitro and their effects on the proliferation and migration of skin fibroblasts (FB) were evaluated. The expression levels of NORAD, miR-524-5p and Pumilio were analyzed by fluorescence quantitative PCR. Pumilio protein was silenced by siRNA technique to evaluate its role in ADSC exosome-mediated wound healing. The experimental results showed that under hypoxia conditions, NORAD levels in ADSC exosomes increased significantly and could effectively regulate the expression of miR-524-5p. After Pumilio protein silencing, the proliferation and migration ability of fibroblasts were significantly reduced, indicating that Pumilio protein played a role in the process of wound healing. By inhibiting miR-524-5p, the expression of Pumilio protein was restored, further confirming its regulatory mechanism.