Exosomes derived from BMSCs enhance diabetic wound healing through circ-Snhg11 delivery
Abstract Background Exosomes (Exos) generated from bone mesenchymal stem cells (BMSCs) are elucidated to enhance cutaneous wound healing in mice models of diabetes mellitus (DM). While underlying mechanisms remain unknown. Methods Next-generation sequencing (NGS) was used to examine changes in circR...
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BMC
2024-02-01
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Series: | Diabetology & Metabolic Syndrome |
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Online Access: | https://doi.org/10.1186/s13098-023-01210-x |
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author | Tao Tang Linyi Chen Ming Zhang Chuang Wang Xiaolong Du Shenglin Ye Xiaoqiang Li Hong Chen Nan Hu |
author_facet | Tao Tang Linyi Chen Ming Zhang Chuang Wang Xiaolong Du Shenglin Ye Xiaoqiang Li Hong Chen Nan Hu |
author_sort | Tao Tang |
collection | DOAJ |
description | Abstract Background Exosomes (Exos) generated from bone mesenchymal stem cells (BMSCs) are elucidated to enhance cutaneous wound healing in mice models of diabetes mellitus (DM). While underlying mechanisms remain unknown. Methods Next-generation sequencing (NGS) was used to examine changes in circRNA expression levels following Exo treatment. Luciferase assays were used to determine the interactions between RNAs. Immunofluorescence staining was used to examine reactive oxygen species (ROS) in endothelial progenitor cells (EPCs) cultured in high glucose (HG) conditions. Therapeutic effects regarding Exos were also examined by immunofluorescence. Results We found that Exo treatment enhanced cutaneous wound healing significantly. NGS indicated that circ-Snhg11 was involved in Exo-mediated tissue repairing. Downregulation of circ-Snhg11 decreased Exo-mediated therapy responses during wound healing in diabetic mouse. Our luciferase reporter data confirmed that SLC7A11 and miR-144-3p were circ-Snhg11 downstream targets. miR-144-3p overexpression or SLC7A11 knockdown altered the protective effects of circ-Snhg11 upon EPCs exposed to HG conditions. Upregulation of circ-Snhg11 incremented therapy effects of Exo treatment during wound healing in DM mice through enhanced angiogenesis along with a reduction in GPX4-mediated ferroptosis. Conclusions circ-Snhg11 in BMSC-Exos enhanced SLC7A11/GPX4-mediated anti-ferroptosis signals via miR-144-3p sponging resulting in enhanced diabetic wound healing and improved angiopoiesis. |
first_indexed | 2024-03-07T14:49:10Z |
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institution | Directory Open Access Journal |
issn | 1758-5996 |
language | English |
last_indexed | 2024-03-07T14:49:10Z |
publishDate | 2024-02-01 |
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series | Diabetology & Metabolic Syndrome |
spelling | doaj.art-fed7d6f81b2e4af18bee1b409c901c482024-03-05T19:49:15ZengBMCDiabetology & Metabolic Syndrome1758-59962024-02-0116111210.1186/s13098-023-01210-xExosomes derived from BMSCs enhance diabetic wound healing through circ-Snhg11 deliveryTao Tang0Linyi Chen1Ming Zhang2Chuang Wang3Xiaolong Du4Shenglin Ye5Xiaoqiang Li6Hong Chen7Nan Hu8Department of Vascular Surgery, The Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical SchoolDepartment of Ophthalmology, The Fourth Affiliated Hospital of Nanjing Medical UniversityDepartment of Vascular Surgery, The Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical SchoolDepartment of Vascular Surgery, The Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical SchoolDepartment of Vascular Surgery, The Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical SchoolDepartment of Vascular Surgery, The Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical SchoolDepartment of Vascular Surgery, The Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical SchoolDepartment of Vascular Surgery, The Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical SchoolDepartment of Vascular Surgery, The Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical SchoolAbstract Background Exosomes (Exos) generated from bone mesenchymal stem cells (BMSCs) are elucidated to enhance cutaneous wound healing in mice models of diabetes mellitus (DM). While underlying mechanisms remain unknown. Methods Next-generation sequencing (NGS) was used to examine changes in circRNA expression levels following Exo treatment. Luciferase assays were used to determine the interactions between RNAs. Immunofluorescence staining was used to examine reactive oxygen species (ROS) in endothelial progenitor cells (EPCs) cultured in high glucose (HG) conditions. Therapeutic effects regarding Exos were also examined by immunofluorescence. Results We found that Exo treatment enhanced cutaneous wound healing significantly. NGS indicated that circ-Snhg11 was involved in Exo-mediated tissue repairing. Downregulation of circ-Snhg11 decreased Exo-mediated therapy responses during wound healing in diabetic mouse. Our luciferase reporter data confirmed that SLC7A11 and miR-144-3p were circ-Snhg11 downstream targets. miR-144-3p overexpression or SLC7A11 knockdown altered the protective effects of circ-Snhg11 upon EPCs exposed to HG conditions. Upregulation of circ-Snhg11 incremented therapy effects of Exo treatment during wound healing in DM mice through enhanced angiogenesis along with a reduction in GPX4-mediated ferroptosis. Conclusions circ-Snhg11 in BMSC-Exos enhanced SLC7A11/GPX4-mediated anti-ferroptosis signals via miR-144-3p sponging resulting in enhanced diabetic wound healing and improved angiopoiesis.https://doi.org/10.1186/s13098-023-01210-xExosomesDiabetic wound healingBone mesenchymal stem cellscirc-Snhg11Endothelial progenitor cells (EPCs) |
spellingShingle | Tao Tang Linyi Chen Ming Zhang Chuang Wang Xiaolong Du Shenglin Ye Xiaoqiang Li Hong Chen Nan Hu Exosomes derived from BMSCs enhance diabetic wound healing through circ-Snhg11 delivery Diabetology & Metabolic Syndrome Exosomes Diabetic wound healing Bone mesenchymal stem cells circ-Snhg11 Endothelial progenitor cells (EPCs) |
title | Exosomes derived from BMSCs enhance diabetic wound healing through circ-Snhg11 delivery |
title_full | Exosomes derived from BMSCs enhance diabetic wound healing through circ-Snhg11 delivery |
title_fullStr | Exosomes derived from BMSCs enhance diabetic wound healing through circ-Snhg11 delivery |
title_full_unstemmed | Exosomes derived from BMSCs enhance diabetic wound healing through circ-Snhg11 delivery |
title_short | Exosomes derived from BMSCs enhance diabetic wound healing through circ-Snhg11 delivery |
title_sort | exosomes derived from bmscs enhance diabetic wound healing through circ snhg11 delivery |
topic | Exosomes Diabetic wound healing Bone mesenchymal stem cells circ-Snhg11 Endothelial progenitor cells (EPCs) |
url | https://doi.org/10.1186/s13098-023-01210-x |
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