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Exosomes derived from mmu_circ_0000250-modified adipose-derived mesenchymal stem cells promote wound healing in diabetic mice by inducing miR-128-3p/SIRT1-mediated autophagy.
Shi, Rongfeng; Jin, Yinpeng; Hu, Weiwei; Lian, Weishuai; Cao, Chuanwu; Han, Shilong; Zhao, Suming; Yuan, Hongxin; Yang, Xiaohu; Shi, Jiahai; Zhao, Hui.
Afiliación
  • Shi R; Department of Interventional Radiology, Affiliated Hospital of Nantong University, Nantong, People's Republic of China.
  • Jin Y; Shanghai Public Health Clinical Center, Fudan University, Shanghai, People's Republic of China.
  • Hu W; Science and Technology Innovation Center of Guangzhou University of Traditional Chinese Medicine, Guangzhou, People's Republic of China.
  • Lian W; Sanyuanli Campus of Guangzhou University of Traditional Chinese Medicine, Guangzhou, People's Republic of China.
  • Cao C; Department of Interventional and Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, People's Republic of China.
  • Han S; Institute of Medical Intervention Engineering, Tongji University, Shanghai, People's Republic of China.
  • Zhao S; Department of Interventional and Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, People's Republic of China.
  • Yuan H; Institute of Medical Intervention Engineering, Tongji University, Shanghai, People's Republic of China.
  • Yang X; Department of Interventional and Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, People's Republic of China.
  • Shi J; Institute of Medical Intervention Engineering, Tongji University, Shanghai, People's Republic of China.
  • Zhao H; Department of Interventional Radiology, Affiliated Hospital of Nantong University, Nantong, People's Republic of China.
Am J Physiol Cell Physiol ; 318(5): C848-C856, 2020 05 01.
Article en En | MEDLINE | ID: mdl-32159361
More and more evidence advises that circular RNAs (circRNAs) function critically in regulating different disease microenvironments. Our previous study found that autotransplantation of adipose-derived mesenchymal stem cells (ADSCs) promotes diabetes wound healing. Exosomes derived in ADSCs play an important regulatory role. This study aimed to characterize if mmu_circ_0000250 played a role in ADSC-exosome-mediated full-thickness skin wound repair in diabetic rats. Endothelial progenitor cells (EPCs) were selected to study the therapeutic mechanism of exosomes in high-glucose (HG)-induced cell damage and dysfunction. Analysis and luciferase reporter assay were utilized to explore the interaction among mmu_circ_0000250, miRNA (miR)-128-3p, and sirtuin (SIRT)1. The diabetic rats were used to confirm the therapeutic effect of mmu_circ_0000250 against exosome-mediated wound healing. Exosomes containing a high concentration of mmu_circ_0000250 had a greater therapeutic effect on restoration of the function of EPCs by promotion autophagy activation under HG conditions. Expression of mmu_circ_0000250 promoted SIRT1 expression by miR-128-3p adsorption, which was confirmed via luciferase reporter assay and bioinformatics analysis. In vivo, exosomes containing a high concentration of mmu_circ_0000250 had a more therapeutic effect on wound healing when compared with wild-type exosomes from ADSCs. Immunohistochemistry and immunofluorescence detection showed that mmu_circ_0000250 increased angiopoiesis with exosome treatment in wound skin and suppressed apoptosis by autophagy activation. In conclusion, we verified that mmu_circ_0000250 enhanced the therapeutic effect of ADSC-exosomes to promote wound healing in diabetes by absorption of miR-128-3p and upregulation of SIRT1. Therefore, these findings advocate targeting the mmu_circ_0000250/miR-128-3p/SIRT1 axis as a candidate therapeutic option for diabetic ulcers.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Úlcera / MicroARNs / Diabetes Mellitus Experimental / Sirtuina 1 / ARN Circular Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Am J Physiol Cell Physiol Asunto de la revista: FISIOLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Úlcera / MicroARNs / Diabetes Mellitus Experimental / Sirtuina 1 / ARN Circular Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Am J Physiol Cell Physiol Asunto de la revista: FISIOLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos