Exosomes Derived from E2F1–/– Adipose-Derived Stem Cells Promote Skin Wound Healing via miR-130b-5p/TGFBR3 Axis

作者：Honghao Yu, Yiping Wu, Boyu Zhang, Mingchen Xiong, Yi Yi, Qi Zhang, Min Wu · 发表于：International Journal of Nanomedicine · 年份：2023 · DOI：10.2147/ijn.s431725 · 被引用次数：31 · 研究领域：Extracellular vesicles in disease、Wound Healing and Treatments、MicroRNA in disease regulation

Background: Skin wound is a widespread health problem and brings extraordinary burdens to patients. Exosomes derived from adipose-derived stem cells (ADSC-Exos) are considered promising strategies for repairing skin wounds. E2F1 is a member of the E2F family of transcription factors involved in cell growth and apoptosis. E2F1 deficiency in mice enhances wound healing by improving collagen deposition and angiogenesis. Additionally, E2F1 can regulate the transcription and paracrine activity of multiple miRNAs, which will inevitably reshape the paracrine expression profile of ADSC-Exos. This study aimed to investigate the impact of transcription factor E2F1 deficiency on the functions of ADSC-Exos in promoting wound healing. Methods: First, we obtained ADSCs from subcutaneous adipose tissues of WT and E2F1 –/– C57BL/6 mice and separated their exosomes, denoted as ADSC WT -Exos and ADSC E2F1-/- -Exos. The wound healing effects of ADSC WT -Exos and ADSC E2F1-/- -Exos in full-thickness skin wound models were investigated by wound images, H&E staining, and immunohistochemical staining. For the in vitro study, the abilities of ADSC WT -Exos and ADSC E2F1-/- -Exos to promote cell activities, collagen formation, and angiogenesis were evaluated. The potential mechanism by which ADSC E2F1-/- -Exos promote wound healing was determined by miRNA sequencing, ChIP‒qPCR, and dual-luciferase assays. Results: ADSC E2F1-/- -Exos accelerated wound healing by promoting collagen formation and angiog...