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Exosomal circHIPK3 derived from umbilical cord‐derived mesenchymal stem cells enhances skin fibroblast autophagy by blocking miR‐20b‐5p/ULK1/Atg13 axis

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 glu...

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Autores principales: Qiu, Zhi‐Yang, Lin, Shi‐Shuai, Pan, Nan‐Fang, Lin, Zhi‐Hu, Pan, Yun‐Chuan, Liang, Zun‐Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688123/
https://www.ncbi.nlm.nih.gov/pubmed/37688345
http://dx.doi.org/10.1111/jdi.14077
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author Qiu, Zhi‐Yang
Lin, Shi‐Shuai
Pan, Nan‐Fang
Lin, Zhi‐Hu
Pan, Yun‐Chuan
Liang, Zun‐Hong
author_facet Qiu, Zhi‐Yang
Lin, Shi‐Shuai
Pan, Nan‐Fang
Lin, Zhi‐Hu
Pan, Yun‐Chuan
Liang, Zun‐Hong
author_sort Qiu, Zhi‐Yang
collection PubMed
description 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.
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spelling pubmed-106881232023-12-01 Exosomal circHIPK3 derived from umbilical cord‐derived mesenchymal stem cells enhances skin fibroblast autophagy by blocking miR‐20b‐5p/ULK1/Atg13 axis Qiu, Zhi‐Yang Lin, Shi‐Shuai Pan, Nan‐Fang Lin, Zhi‐Hu Pan, Yun‐Chuan Liang, Zun‐Hong J Diabetes Investig Articles 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. John Wiley and Sons Inc. 2023-09-08 /pmc/articles/PMC10688123/ /pubmed/37688345 http://dx.doi.org/10.1111/jdi.14077 Text en © 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Articles
Qiu, Zhi‐Yang
Lin, Shi‐Shuai
Pan, Nan‐Fang
Lin, Zhi‐Hu
Pan, Yun‐Chuan
Liang, Zun‐Hong
Exosomal circHIPK3 derived from umbilical cord‐derived mesenchymal stem cells enhances skin fibroblast autophagy by blocking miR‐20b‐5p/ULK1/Atg13 axis
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 Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688123/
https://www.ncbi.nlm.nih.gov/pubmed/37688345
http://dx.doi.org/10.1111/jdi.14077
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