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Research Article

LncRNA MALAT1 from human adipose-derived stem cell exosomes accelerates wound healing via miR-378a/FGF2 axis

    Li Pi

    Department of Burn & Plastic Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, P.R. China

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    ,
    Li Yang

    Department of Burn & Plastic Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, P.R. China

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    ,
    Bai-Rong Fang

    Department of Burn & Plastic Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, P.R. China

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    ,
    Xian-Xi Meng

    Department of Burn & Plastic Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, P.R. China

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    &
    Li Qian

    *Author for correspondence: Tel.: +86 158 7485 9977;

    E-mail Address: 616067028@csu.edu.cn

    Department of Burn & Plastic Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, P.R. China

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    Published Online:13 Jul 2022https://doi.org/10.2217/rme-2021-0170

    Abstract

    Aim: The effects of MALAT1 from human adipose-derived stem cell (ADSC) exosomes in skin wound healing were investigated. Material & methods: The viability, apoptosis and migration ability of human skin fibroblasts (HSFs) were evaluated by Cell Counting Kit-8 assay, flow cytometry and scratch assay, respectively. A mouse model was established to evaluate the role of exosomal MALAT1 in skin wound healing in vivo. Results: Human ADSC exosomes promoted the proliferation and migration of HSFs and increased MALAT1 expression. MALAT1 silencing in human ADSCs inhibited HSF viability and migration, promoted HSF apoptosis and inhibited angiogenesis by upregulating miR-378a. Overexpression of miR-378a inhibited the migration and proliferation of HSFs by downregulating FGF2 expression. ADSC exosomes promoted skin wound healing by mediating MALAT1 in vivo. Conclusion: Exosomal MALAT1 accelerated skin wound healing by regulating the miR-378a/FGF2 axis, suggesting that MALAT1 might be used as a potential target for cutaneous wound treatment.

    Graphical abstract

    Plain language summary

    Skin wound healing is a process of synergistic action of multiple factors. Adipose-derived stem cells (ADSCs), a group of stem cells, are recruited into damaged tissues and secret several cytokines, which promote nascent tissue formation. ADSC-derived exosomes play crucial roles in wound healing as a paracrine vehicle for delivering chemokines, growth factors and RNAs to host cells. LncRNAs are involved in multiple physiological processes, including tissue repair. Furthermore, lncRNA MALAT1 is associated with endothelial cell migration and angiogenesis in different types of diseases. This study demonstrated that hADSC exosomes promoted the proliferation and migration of human skin fibroblasts and increased MALAT1 expression. MALAT1 silencing in human ADSCs inhibited human skin fibroblast viability and migration, promoted apoptosis and suppressed angiogenesis by upregulating miR-378a. miR-378a overexpression inhibited the phenotypic characteristics of human skin fibroblasts by downregulating FGF2. Exosomal MALAT1 appeared to accelerate skin wound healing by mediating the miR-378a/FGF2 axis.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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