Rosiglitazone accelerates wound healing by improving endothelial precursor cell function and angiogenesis in db/db mice

Guoliang Zhou; Xue Han; Zhiheng Wu; Qiaojuan Shi; Xiaogang Bao

doi:10.7717/peerj.7815

Rosiglitazone accelerates wound healing by improving endothelial precursor cell function and angiogenesis in db/db mice

PeerJ. 2019 Oct 17:7:e7815. doi: 10.7717/peerj.7815. eCollection 2019.

Authors

Guoliang Zhou^#¹, Xue Han^#², Zhiheng Wu³, Qiaojuan Shi², Xiaogang Bao⁴

Affiliations

¹ Department of Pharmacy, School of Life and Health Sciences, Anhui Science and Technology University, Fengyang, Anhui, China.
² Laboratory Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang Province, China.
³ School of Clinical Medicine, Wannan Medicial Colledge, Wuhu, Anhui, China.
⁴ Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Second Military Medical University, Shanghai, China.

^# Contributed equally.

Abstract

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.

Keywords: Angiogenesis; Diabetes mellitus; Endothelial precursor cell; Rosiglitazone; Vascular endothelial growth factor; Wound healing.

Grants and funding

This study was supported by the Natural Science Foundation of Zhejiang (Grants LGJ18H310002 and LQY19H090001), National Natural Science Foundation of China (No. 31900381 and 31870080), the Medical Scientific Research Foundation of Zhejiang Province (No. 2020388156), the Youth start-up fund of Second Military Medical University (Grant No. 2018QN13), and the Innovation Training Program of Anhui (No. 201810368117). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.