BMSC derived exosomes accelerate diabetic wound healing via circ-Snhg11 delivery

Background: Exosome (Exo) secreted by bone mesenchymal stem cells (BMSCs) enhances cutaneous wound healing in mouse with diabetes mellitus (DM). However, the mechanism remains unclear. Methods: : Next-generation sequencing (NGS) was applied to study abnormal circular RNA (circRNA) expressions in ulcer tissues with or without Exo treatment. Bioinformatics and luciferase outputs were employed to verify interactional correlations amongst RNAs. EPCs cells were utilized to study the ROS under high glucose conditions by immunofluorescence. A DM ulceration mouse model was established and the therapeutic Exo effect was investigated through immunofluorescence. Results: : Data showcased that Exo treatment significantly promoted cutaneous wound healing in mice with DM. NGS discovered that circ-Snhg11 functioned in Exo-mediated tissues repair. circ-Snhg11 downregulation reduced therapeutic effects regarding Exo upon wound healing in diabetic mice. Bioinformatics and luciferase reporting outcomes verified that both miR-144-3p and SLC7A11 were circ-Snhg11 downstream targets. SLC7A11 downregulation or miR-144-3p overexpression reversed protective effect regarding circ-Snhg11 on EPCs after exposure to a high glucose microenvironment. circ-Snhg11 upregulation increased the therapeutic Exo effect on wound healing in diabetic mice by stimulating angiogenesis and reducing GPX4-mediated ferroptosis. Furthermore, Exo circ-Snhg11 delivery promoted the miR-144-3p/SLC7A11/GPX4 signal. Conclusions: : In conclusion, circ-Snhg11 from BMSC Exo promoted the SLC7A11/GPX4-mediated anti-ferroptosis signal by sponging miR-144-3p. This promoted angiopoiesis and accelerated diabetic wound healing.