Abstract
Cutaneous wound is a soft tissue injury that is difficult to heal during aging. It has been demonstrated that adipose-derived stem cells (ADSCs) and its secreted exosomes exert crucial functions in cutaneous wound healing. The present study aimed to elucidate the mechanism of exosomes derived from ADSCs (ADSC-Exos) containing MALAT1 in wound healing. ADSCs were isolated from human normal subcutaneous adipose tissues and identified by flow cytometry analysis. Exosomes were extracted from ADSC supernatants and MALAT1 expression was determined using qRT-PCR analysis. HaCaT and HDF cells were exposed to hydrogen peroxide (H2O2) for simulating the skin lesion model. Subsequently, CCK-8, flow cytometry, wound healing and transwell assays were employed to validate the role of ADSC-Exos containing MALAT1 in the skin lesion model. Besides, cells were transfected with sh-MALAT1 to verify the protective role of MALAT1 in wound healing. The binding relationship between MALAT1 and miR-124 were measured by dual-luciferase reporter assay. ADSC-Exos promoted cell proliferation, migration, and inhibited cell apoptosis of HaCaT and HDF cells impaired by H2O2. However, the depletion of MALAT1 in ADSC-Exos lose these protective effects on HaCaT and HDF cells. Moreover, miR-124 was identified to be a target of MALAT1. Furthermore, ADSC-Exos containing MALAT1 could mediate H2O2-induced wound healing by targeting miR-124 and activating Wnt/β-catenin pathway. ADSC-Exos containing MALAT1 play a positive role in cutaneous wound healing possibly via targeting miR-124 through activating the Wnt/β-catenin pathway, which may provide novel insights into the therapeutic target for cutaneous wound healing.
Highlights
Cutaneous wound healing is a dynamic process and involves four precisely integrated and overlapping phases, including hemostasis, inflammation, proliferation and tissue remodeling [1,2]
We demonstrated that adipose-derived stem cell (ADSC)-Exos containing metastasis associated lung adenocarcinoma transcript 1 (MALAT1) significantly attenuated hydrogen peroxide (H2O2)-induced the suppression of cell proliferation, migration and the promotion of apoptosis via targeting miR-124 through Wnt/β-catenin pathway
Exosomes purified from ADSCs culture supernatants were characterized by transmission electron microscopy (TEM), and the results showed that exosomes were round membrane-bound vesicles with 30–100 nm diameter (Supplementary Figure S2)
Summary
Cutaneous wound healing is a dynamic process and involves four precisely integrated and overlapping phases, including hemostasis, inflammation, proliferation and tissue remodeling [1,2]. In the process of skin wound healing, the integration of skin cell differentiation, migration, proliferation and apoptosis plays a crucial role in skin tissue repair [5]. The wound after healing has the characteristic of regenerative epithelialization, which is related to two basic functions of keratinocytes, namely proliferation and migration [6]. Some growth factors, such as transforming growth factor β (TGF-β) and epidermal growth factor (EGF), can stimulate cell proliferation, differentiation and migration. Many signaling pathways play crucial role during cutaneous wound repair: the Wnt/β-catenin, Notch, Hedgehog and various growth factor/cytokine pathways [7] The functions of these growth factors and signaling pathways in clinical
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