The efficacy of miR-141-3p to facilitate the healing of wounds and prevent scarring in mice by blocking the JNK/ERK pathway via HDAC6 silencing.

Abstract

Purpose: Adipose-derived mesenchymal stem cells (ADSCs) exosomes (AD-Exos) are a novel and promising therapeutic approach for skin damage repair. This investigation seeks to assess the potential clinical utility of miR-141-3p found in AD-exos for expediting wound healing.

Methods: ADSCs were isolated from the wounded patients' tissue and validated via flow cytometry, and the mineralization and adipogenic capabilities of ADSCs were assessed respectively. Additionally, exosomes were isolated and identified. miR-141-3p and HDAC6.protein level were tested. Full-thickness wound models were created on the backs of mice, HE staining, ELISA, and immunohistochemistry were used to assess the influences of AD-exos on wound healing, inflammation, and new blood vessel formation Western blot was to assess the related-protein levels of JNK/ERK pathway. AQ1 Meanwhile, Dual-Luciferase assay confirmed the relationship between miR-141-3p and HDAC6.

Results: The isolated cells highly express surface markers of mesenchymal stem cells and possess the potential for multidirectional differentiation, confirming them to be ADSCs. And miR-141-3p down-regulated but HDAC6 up-regulated in the serum and AD-exos of wounded patients. miR-141-3p could negatively modulate HDAC6. The miR-141-3p in AD-exos accelerated wound healing in mice, mitigated inflammatory responses and scarring in the injured skin tissue, and promoted angiogenesis, moreover, AD-exos could diminish the phosphorylation of JNK and ERK, while HDAC6 overexpressed could weaken these impacts.

Conclusion: miR-141-3p in AD-exos can target down regulate HDAC6 expression and inhibit JNK/ERK signaling pathway activation, thereby reducing wound inflammation and promoting angiogenesis and wound healing in mice.