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Journal of Diabetes Research
Volume 2019, Article ID 1897174, 10 pages
https://doi.org/10.1155/2019/1897174
Research Article

Von Hippel-Lindau (VHL) Protein Antagonist VH298 Improves Wound Healing in Streptozotocin-Induced Hyperglycaemic Rats by Activating Hypoxia-Inducible Factor- (HIF-) 1 Signalling

Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

Correspondence should be addressed to Jia Xu; moc.621@7110aijux, Gen Wen; moc.621@6002negnew, and Yimin Chai; nc.ude.utjs@iahcmy

Received 27 June 2018; Revised 1 November 2018; Accepted 29 November 2018; Published 17 February 2019

Academic Editor: Sergiu Catrina

Copyright © 2019 Shuo Qiu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Aims. The purpose of the present research is to investigate the effects of the VHL protein antagonist, VH298, on functional activities of fibroblasts and vascular endothelial cells and the effects on the wound healing process in a streptozotocin-induced hyperglycaemic rat model. Methods. HIF-1α and hydroxy-HIF-1α protein levels in VH298-treated rat fibroblasts (rFb) were measured by immunoblotting, rFb proliferation was detected by the CCK-8 assay, and mRNA levels of related genes were measured by quantitative RT-PCR. In vitro wound healing was simulated by the scratch test; angiogenesis was measured by the human umbilical vein endothelial cell (hUVEC) tube formation assay. VH298 or PBS was locally injected into wounds in rat models with streptozotocin- (STZ-) induced hyperglycaemia, the wound tissues were harvested, and haematoxylin-eosin (HE) and Masson trichrome staining and immunohistochemical processes were conducted. Results. HIF-1α and hydroxy-HIF-1α levels increased in VH298-treated rFb, in a time- and dose-dependent manner. Thirty micromolar VH298 could significantly increase cell proliferation, angiogenesis, and gene expression of type I collagen-α1 (Col1-α1), vascular endothelial growth factor A (VEGF-A), and insulin-like growth factor 1 (IGF-1). The VH298-treated wound had a better healing pattern, activation of HIF-1 signalling, and vascularization. Conclusions. Taken together, VH298 activated the HIF-1 signalling pathway by stabilizing both HIF-1α and hydroxy-HIF-1α. VH298 enhanced rFb functions, promoted hUVEC angiogenesis, and accelerated wound healing in the rat model mimicking diabetes mellitus.