A therapeutic role of exosomal lncRNA H19 from adipose mesenchymal stem cells in cutaneous wound healing by triggering macrophage M2 polarization

Emerging evidence has figured out that adipose mesenchymal stem cells (ADSCs) promote wound healing. Exosomes, which act as main paracrine factors and contains various protein, lncRNA, and miRNAs, play a critical role in wound healing. Nevertheless, the mechanism remains to be elucidated. This study aims to identify the underlying mechanism of ADSCs-derived exosome (ADSCs-exos)-mediated wound healing. ADSCs-exos were characterized using the transmission electron microscope, dynamic light scattering, and western blot. ELISA, RT-qPCR, flow cytometry, western blot, CCK-8 assay, transwell assay and tube formation were employed to validate the actions of ADSCs-exos harboring H19 in cell polarization, proliferation, migration and angiogenesis. The regulatory axis among H19, miR-130b-3p and PPARγ or STAT3 was confirmed by RNA pull-down, RIP assay and dual-luciferase reporter assays. ADSCs-exos harboring H19 promoted macrophage M2 polarization, thereby enhancing fibroblast proliferation, migration and endothelial cell angiogenesis. However, their promotive effects were disrupted within H19 depletion in ADSCs-exos. Additionally, miR-130b-3p, directly targeting PPARγ or STAT3, was identified to be a downstream effector to participate in H19-mediated biological effects. Moreover, ADSCs-exos carrying H19 modulated cutaneous wound healing via H19/miR-130b-3p -mediated macrophage M2 polarization in vivo. Collectively, ADSCs-derived exosomal H19 accelerates cutaneous wound healing via the miR-130b-3p/PPARγ/STAT3 axis, indicating potential therapeutic strategies for the treatment of wound healing.