Exosomal circHIPK3 derived from umbilical cord‐derived mesenchymal stem cells enhances skin fibroblast autophagy by blocking miR‐20b‐5p/ULK1/Atg13 axis
ABSTRACT Background Umbilical cord‐derived mesenchymal stem cells (UCMSCs) could alleviate diabetes‐induced injury. Hence, this investigation aimed to explore the role and mechanism of UCMSCs‐derived exosomal circHIPK3 (exo‐circHIPK3) in diabetes mellitus (DM). Methods HFF‐1 cells were cultured in h...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | Journal of Diabetes Investigation |
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| Online Access: | https://doi.org/10.1111/jdi.14077 |
| _version_ | 1797447686818889728 |
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| author | Zhi‐Yang Qiu Shi‐Shuai Lin Nan‐Fang Pan Zhi‐Hu Lin Yun‐Chuan Pan Zun‐Hong Liang |
| author_facet | Zhi‐Yang Qiu Shi‐Shuai Lin Nan‐Fang Pan Zhi‐Hu Lin Yun‐Chuan Pan Zun‐Hong Liang |
| author_sort | Zhi‐Yang Qiu |
| collection | DOAJ |
| description | ABSTRACT Background Umbilical cord‐derived mesenchymal stem cells (UCMSCs) could alleviate diabetes‐induced injury. Hence, this investigation aimed to explore the role and mechanism of UCMSCs‐derived exosomal circHIPK3 (exo‐circHIPK3) in diabetes mellitus (DM). Methods HFF‐1 cells were cultured in high glucose (HG) medium or normal medium, and treated with UCMSCs‐derived exo‐circHIPK3 or miR‐20b‐5p mimics or Unc‐51‐like autophagy activating kinase 1 (ULK1) overexpression vector. The surface markers of UCMSCs were analyzed using a flow cytometer. The differentiation potential of UCMSCs was evaluated using oil red O staining, alizarin red staining and alkaline phosphatase (ALP) staining. Cell proliferation was determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The miRNA expressions were analyzed by reverse transcription‐quantitative polymerase chain reaction (qRT‐PCR). Protein levels were quantified by western blot. An immunofluorescence staining was used for observing LC3 expression. The interaction between miR‐20b‐5p and circHIPK3, and between miR‐20b‐5b and ULK1 were identified by a RNA immunoprecipitation (RIP) assay and a luciferase reporter assay. Results Up‐regulation of circHIPK3 was found in UCMSCs‐derived exosomes. Exo‐circHIPK3 decreased the miR‐20b‐5p level while increasing the contents of ULK1 and autophagy‐related gene 13 (Atg13) in HG‐induced fibroblasts. In addition, exo‐circHIPK3 activated HG‐induced fibroblast autophagy and proliferation. Overexpressed miR‐20b‐5p promoted fibroblast injury by inhibiting cell autophagy via the ULK1/Atg13 axis in HG conditions of high glucose. Moreover, exo‐circHIPK3 enhanced autophagy and cell viability in HG‐induced fibroblasts through the miR‐20b‐5p/ULK1/Atg13 axis. Conclusion UCMSCs‐derived exosomal circHIPK3 promoted cell autophagy and proliferation and accelerated the fibroblast injury repair by the miR‐20b‐5p/ULK1/Atg13 axis. |
| first_indexed | 2024-03-09T13:59:30Z |
| format | Article |
| id | doaj.art-ee3c0ae3bb3742abbabd356081f75e3b |
| institution | Directory Open Access Journal |
| issn | 2040-1116 2040-1124 |
| language | English |
| last_indexed | 2024-03-09T13:59:30Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Investigation |
| spelling | doaj.art-ee3c0ae3bb3742abbabd356081f75e3b2023-11-30T11:41:37ZengWileyJournal of Diabetes Investigation2040-11162040-11242023-12-0114121344135510.1111/jdi.14077Exosomal circHIPK3 derived from umbilical cord‐derived mesenchymal stem cells enhances skin fibroblast autophagy by blocking miR‐20b‐5p/ULK1/Atg13 axisZhi‐Yang Qiu0Shi‐Shuai Lin1Nan‐Fang Pan2Zhi‐Hu Lin3Yun‐Chuan Pan4Zun‐Hong Liang5Department of Burn & Skin Repair Surgery Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University) Haikou Hainan ChinaDepartment of Burn & Skin Repair Surgery Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University) Haikou Hainan ChinaDepartment of Burn & Skin Repair Surgery Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University) Haikou Hainan ChinaDepartment of Burn & Skin Repair Surgery Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University) Haikou Hainan ChinaDepartment of Burn & Skin Repair Surgery Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University) Haikou Hainan ChinaDepartment of Burn & Skin Repair Surgery Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University) Haikou Hainan ChinaABSTRACT Background Umbilical cord‐derived mesenchymal stem cells (UCMSCs) could alleviate diabetes‐induced injury. Hence, this investigation aimed to explore the role and mechanism of UCMSCs‐derived exosomal circHIPK3 (exo‐circHIPK3) in diabetes mellitus (DM). Methods HFF‐1 cells were cultured in high glucose (HG) medium or normal medium, and treated with UCMSCs‐derived exo‐circHIPK3 or miR‐20b‐5p mimics or Unc‐51‐like autophagy activating kinase 1 (ULK1) overexpression vector. The surface markers of UCMSCs were analyzed using a flow cytometer. The differentiation potential of UCMSCs was evaluated using oil red O staining, alizarin red staining and alkaline phosphatase (ALP) staining. Cell proliferation was determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The miRNA expressions were analyzed by reverse transcription‐quantitative polymerase chain reaction (qRT‐PCR). Protein levels were quantified by western blot. An immunofluorescence staining was used for observing LC3 expression. The interaction between miR‐20b‐5p and circHIPK3, and between miR‐20b‐5b and ULK1 were identified by a RNA immunoprecipitation (RIP) assay and a luciferase reporter assay. Results Up‐regulation of circHIPK3 was found in UCMSCs‐derived exosomes. Exo‐circHIPK3 decreased the miR‐20b‐5p level while increasing the contents of ULK1 and autophagy‐related gene 13 (Atg13) in HG‐induced fibroblasts. In addition, exo‐circHIPK3 activated HG‐induced fibroblast autophagy and proliferation. Overexpressed miR‐20b‐5p promoted fibroblast injury by inhibiting cell autophagy via the ULK1/Atg13 axis in HG conditions of high glucose. Moreover, exo‐circHIPK3 enhanced autophagy and cell viability in HG‐induced fibroblasts through the miR‐20b‐5p/ULK1/Atg13 axis. Conclusion UCMSCs‐derived exosomal circHIPK3 promoted cell autophagy and proliferation and accelerated the fibroblast injury repair by the miR‐20b‐5p/ULK1/Atg13 axis.https://doi.org/10.1111/jdi.14077autophagyDMExo‐circHIPK3 |
| spellingShingle | Zhi‐Yang Qiu Shi‐Shuai Lin Nan‐Fang Pan Zhi‐Hu Lin Yun‐Chuan Pan Zun‐Hong Liang Exosomal circHIPK3 derived from umbilical cord‐derived mesenchymal stem cells enhances skin fibroblast autophagy by blocking miR‐20b‐5p/ULK1/Atg13 axis Journal of Diabetes Investigation autophagy DM Exo‐circHIPK3 |
| title | Exosomal circHIPK3 derived from umbilical cord‐derived mesenchymal stem cells enhances skin fibroblast autophagy by blocking miR‐20b‐5p/ULK1/Atg13 axis |
| title_full | Exosomal circHIPK3 derived from umbilical cord‐derived mesenchymal stem cells enhances skin fibroblast autophagy by blocking miR‐20b‐5p/ULK1/Atg13 axis |
| title_fullStr | Exosomal circHIPK3 derived from umbilical cord‐derived mesenchymal stem cells enhances skin fibroblast autophagy by blocking miR‐20b‐5p/ULK1/Atg13 axis |
| title_full_unstemmed | Exosomal circHIPK3 derived from umbilical cord‐derived mesenchymal stem cells enhances skin fibroblast autophagy by blocking miR‐20b‐5p/ULK1/Atg13 axis |
| title_short | Exosomal circHIPK3 derived from umbilical cord‐derived mesenchymal stem cells enhances skin fibroblast autophagy by blocking miR‐20b‐5p/ULK1/Atg13 axis |
| title_sort | exosomal circhipk3 derived from umbilical cord derived mesenchymal stem cells enhances skin fibroblast autophagy by blocking mir 20b 5p ulk1 atg13 axis |
| topic | autophagy DM Exo‐circHIPK3 |
| url | https://doi.org/10.1111/jdi.14077 |
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