Insulin-Containing Wound Dressing Promotes Diabetic Wound Healing Through Stabilizing HIF-1α.

Peilang Yang,Xiong Zhang,Tianyi Yu,Dan Liu,Mingzhong Li,Yan Liu,Min Gao,Yan Shi,Jie Zhang,Di Wang,Jizhuang Wang

doi:10.3389/fbioe.2020.592833

Abstract

HIF-1α is seen as a major regulator during wound healing and controls many wound healing processes, such as angiogenesis, extracellular deposition, and reepithelialization. A diabetic state plays a vicious effect on wound healing, and the destabilization of HIF-1α is a non-negligible factor. Insulin-loaded silk fibroin microparticles were prepared to release insulin by covering the wounds, and this material was proven to promote wound healing in both in vitro and in vivo studies. In this work, we found that this insulin-containing wound dressing could accelerate diabetic wound healing by promoting reepithelialization, angiogenesis, and extracellular matrix, especially collagen deposition. Meanwhile, HIF-1α was stable and accumulated in insulin-containing dressing to group wound cells, which was significantly unstable in the control group. In further studies, we showed that methylglyoxal (MGO), the main form of advanced glycation end products (AGEs), accumulated significantly and caused the destabilization of HIF-1α in the diabetic state. Insulin could alleviate the MGO-induced HIF-1α unstable state and promote HIF-1α target gene expression and its downstream biological effect such as angiogenesis and wound extracellular matrix deposition.

Highlights

Diabetic non-healing wound is one of the most common late complication of diabetic patients
When forming a transcription complex with HIF-1β, the co-activator CBP initiates a number of gene expression targets to inflammation reaction, angiogenesis, reepithelialization, and extracellular matrix deposition (Zhao et al, 2012)
Our results show that MGO affects the stability of HIF-1α and decreases the binding of HIF-1α and CBP

Summary

Introduction

Diabetic non-healing wound is one of the most common late complication of diabetic patients. The morbidity rate of diabetic non-healing wound ranges from 5 to 20% among all diabetic patients. Diabetic wound puts a huge pressure on the social health economic system for its retarded healing characteristic (Falanga, 2005; Davis et al, 2018). Diabetic wound shows the characteristics of impaired angiogenesis, reepithelialization, and extracellular matrix deposition (Demidova-Rice et al, 2012). All these characteristics are related to an unstable HIF-1α in the diabetic environment. HIF-1α is considered as the central regulator of wound healing, and it dominates wound healing processes, such as inflammation reaction, angiogenesis, reepithelialization, and extracellular matrix deposition (Hong et al, 2014)

Methods

Results

Conclusion