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/ß-catenin pathway. ADSC-Exos containing MALAT1 play a positive role in cutaneous wound healing possibly via targeting miR-124 through activating the Wnt/ß-catenin pathway, which may provide novel insights into the therapeutic target for cutaneous wound healing.
Subject(s)
Exosomes/metabolism , Fibroblasts/metabolism , Keratinocytes/metabolism , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , Soft Tissue Injuries/metabolism , Stem Cells/metabolism , Subcutaneous Fat/cytology , Wnt Signaling Pathway , Wound Healing , Apoptosis , Cell Movement , Cell Proliferation , Exosomes/genetics , Fibroblasts/drug effects , Fibroblasts/pathology , HaCaT Cells , Humans , Hydrogen Peroxide/toxicity , Keratinocytes/drug effects , Keratinocytes/pathology , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Soft Tissue Injuries/genetics , Soft Tissue Injuries/pathologyABSTRACT
Cretaceous represents one of the hottest greenhouse periods in the Earth's history, but some recent studies suggest that small ice caps might be present in non-polar regions during certain periods in the Early Cretaceous. Here we report extremely negative δ(18)O values of -18.12 to -13.19 for early Aptian hydrothermal zircon from an A-type granite at Baerzhe in northeastern China. Given that A-type granite is anhydrous and that magmatic zircon of the Baerzhe granite has δ(18)O value close to mantle values, the extremely negative δ(18)O values for hydrothermal zircon are attributed to addition of meteoric water with extremely low δ(18)O, mostly likely transported by glaciers. Considering the paleoaltitude of the region, continental glaciation is suggested to occur in the early Aptian, indicating much larger temperature fluctuations than previously thought during the supergreenhouse Cretaceous. This may have impact on the evolution of major organism in the Jehol Group during this period.
