Rosiglitazone accelerates wound healing by improving endothelial precursor cell function and angiogenesis in db/db mice
Background & Aims Endothelial precursor cell (EPC) dysfunction is one of the risk factors for diabetes mellitus (DM) which results in delayed wound healing. Rosiglitazone (RSG) is a frequently prescribed oral glucose-lowering drug. Previous studies have shown the positive effects of RSG on ameli...
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PeerJ Inc.
2019-10-01
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| Online Access: | https://peerj.com/articles/7815.pdf |
| _version_ | 1797424257743978496 |
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| author | Guoliang Zhou Xue Han Zhiheng Wu Qiaojuan Shi Xiaogang Bao |
| author_facet | Guoliang Zhou Xue Han Zhiheng Wu Qiaojuan Shi Xiaogang Bao |
| author_sort | Guoliang Zhou |
| collection | DOAJ |
| description | Background & Aims Endothelial precursor cell (EPC) dysfunction is one of the risk factors for diabetes mellitus (DM) which results in delayed wound healing. Rosiglitazone (RSG) is a frequently prescribed oral glucose-lowering drug. Previous studies have shown the positive effects of RSG on ameliorating EPC dysfunction in diabetic patients. Interestingly, knowledge about RSG with regard to the wound healing process caused by DM is scarce. Therefore, in this study, we investigated the possible actions of RSG on wound healing and the related mechanisms involved in db/db diabetic mice. Methods Db/db mice with spontaneous glucose metabolic disorder were used as a type 2 DM model. RSG (20 mg/kg/d, i.g.,) was administered for 4 weeks before wound creation and bone marrow derived EPC (BM-EPC) isolation. Wound closure was assessed by wound area and CD31 staining. Tubule formation and migration assays were used to judge the function of the BM-EPCs. The level of vascular endothelial growth factor (VEGF), stromal cell derived factor-1α (SDF-1α) and insulin signaling was determined by ELISA. Cell viability of the BM-EPCs was measured by CCK-8 assay. Results RSG significantly accelerated wound healing and improved angiogenesis in db/db mice. Bioactivities of tube formation and migration were decreased in db/db mice but were elevated by RSG. Level of both VEGF and SDF-1α was increased by RSG in the BM-EPCs of db/db mice. Insulin signaling was elevated by RSG reflected in the phosphorylated-to-total AKT in the BM-EPCs. In vitro, RSG improved impaired cell viability and tube formation of BM-EPCs induced by high glucose, but this was prevented by the VEGF inhibitor avastin. Conclusion Our data demonstrates that RSG has benefits for wound healing and angiogenesis in diabetic mice, and was partially associated with improvement of EPC function through activation of VEGF and stimulation of SDF-1α in db/db mice. |
| first_indexed | 2024-03-09T07:59:42Z |
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| language | English |
| last_indexed | 2024-03-09T07:59:42Z |
| publishDate | 2019-10-01 |
| publisher | PeerJ Inc. |
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| series | PeerJ |
| spelling | doaj.art-7e9970aab1124e359ae7bb009e4968f42023-12-03T00:48:49ZengPeerJ Inc.PeerJ2167-83592019-10-017e781510.7717/peerj.7815Rosiglitazone accelerates wound healing by improving endothelial precursor cell function and angiogenesis in db/db miceGuoliang Zhou0Xue Han1Zhiheng Wu2Qiaojuan Shi3Xiaogang Bao4Department of Pharmacy, School of Life and Health Sciences, Anhui Science and Technology University, Fengyang, Anhui, ChinaLaboratory Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang Province, ChinaSchool of Clinical Medicine, Wannan Medicial Colledge, Wuhu, Anhui, ChinaLaboratory Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang Province, ChinaDepartment of Orthopedic Surgery, Spine Center, Changzheng Hospital, Second Military Medical University, Shanghai, ChinaBackground & Aims Endothelial precursor cell (EPC) dysfunction is one of the risk factors for diabetes mellitus (DM) which results in delayed wound healing. Rosiglitazone (RSG) is a frequently prescribed oral glucose-lowering drug. Previous studies have shown the positive effects of RSG on ameliorating EPC dysfunction in diabetic patients. Interestingly, knowledge about RSG with regard to the wound healing process caused by DM is scarce. Therefore, in this study, we investigated the possible actions of RSG on wound healing and the related mechanisms involved in db/db diabetic mice. Methods Db/db mice with spontaneous glucose metabolic disorder were used as a type 2 DM model. RSG (20 mg/kg/d, i.g.,) was administered for 4 weeks before wound creation and bone marrow derived EPC (BM-EPC) isolation. Wound closure was assessed by wound area and CD31 staining. Tubule formation and migration assays were used to judge the function of the BM-EPCs. The level of vascular endothelial growth factor (VEGF), stromal cell derived factor-1α (SDF-1α) and insulin signaling was determined by ELISA. Cell viability of the BM-EPCs was measured by CCK-8 assay. Results RSG significantly accelerated wound healing and improved angiogenesis in db/db mice. Bioactivities of tube formation and migration were decreased in db/db mice but were elevated by RSG. Level of both VEGF and SDF-1α was increased by RSG in the BM-EPCs of db/db mice. Insulin signaling was elevated by RSG reflected in the phosphorylated-to-total AKT in the BM-EPCs. In vitro, RSG improved impaired cell viability and tube formation of BM-EPCs induced by high glucose, but this was prevented by the VEGF inhibitor avastin. Conclusion Our data demonstrates that RSG has benefits for wound healing and angiogenesis in diabetic mice, and was partially associated with improvement of EPC function through activation of VEGF and stimulation of SDF-1α in db/db mice.https://peerj.com/articles/7815.pdfDiabetes mellitusRosiglitazoneEndothelial precursor cellAngiogenesisWound healingVascular endothelial growth factor |
| spellingShingle | Guoliang Zhou Xue Han Zhiheng Wu Qiaojuan Shi Xiaogang Bao Rosiglitazone accelerates wound healing by improving endothelial precursor cell function and angiogenesis in db/db mice PeerJ Diabetes mellitus Rosiglitazone Endothelial precursor cell Angiogenesis Wound healing Vascular endothelial growth factor |
| title | Rosiglitazone accelerates wound healing by improving endothelial precursor cell function and angiogenesis in db/db mice |
| title_full | Rosiglitazone accelerates wound healing by improving endothelial precursor cell function and angiogenesis in db/db mice |
| title_fullStr | Rosiglitazone accelerates wound healing by improving endothelial precursor cell function and angiogenesis in db/db mice |
| title_full_unstemmed | Rosiglitazone accelerates wound healing by improving endothelial precursor cell function and angiogenesis in db/db mice |
| title_short | Rosiglitazone accelerates wound healing by improving endothelial precursor cell function and angiogenesis in db/db mice |
| title_sort | rosiglitazone accelerates wound healing by improving endothelial precursor cell function and angiogenesis in db db mice |
| topic | Diabetes mellitus Rosiglitazone Endothelial precursor cell Angiogenesis Wound healing Vascular endothelial growth factor |
| url | https://peerj.com/articles/7815.pdf |
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