Exosomes derived from autologous dermal fibroblasts promote diabetic cutaneous wound healing through the Akt/β-catenin pathway

Cell Cycle. 2021 Mar-Mar;20(5-6):616-629. doi: 10.1080/15384101.2021.1894813. Epub 2021 Mar 8.

Abstract

Diabetic cutaneous wounds are one of the complications of diabetes mellitus (DM) and are difficult to cure at present. Autologous dermal fibroblasts (DFs) have shown great promise in skin regeneration and repair. However, whether exosomes derived from autologous dermal fibroblasts (DF-Ex) can be used to accelerate diabetic cutaneous wound healing is unclear. In this study, human umbilical vein endothelial cells (HUVECs) were treated with high glucose. We found that DF-Ex could reverse the damage produced by high glucose in HUVECs in vitro. A high-fat diet and streptozotocin were used to establish a rat model of type 2 diabetes mellitus (T2DM), and a diabetic cutaneous wound model was established in the T2DM rats. We discovered that subcutaneous injections of DF-Ex could significantly promote re-epithelialization, collagen deposition, skin cell proliferation, angiogenesis and inhibit inflammation to accelerate diabetic cutaneous wound healing. We further explored the underlying mechanism and found that DF-Ex exerted positive effects by activating the Akt/β-catenin pathway. This research revealed that DF-Ex may provide a new treatment strategy for diabetic cutaneous wound healing.

Keywords: Akt/β-catenin pathway; Exosomes; dermal fibroblasts; diabetic cutaneous wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Autografts / metabolism
  • Autografts / transplantation
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / therapy
  • Exosomes / metabolism*
  • Exosomes / transplantation
  • Fibroblasts / metabolism*
  • Fibroblasts / transplantation
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Male
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Wnt Signaling Pathway / physiology*
  • Wound Healing / physiology*

Substances

  • Proto-Oncogene Proteins c-akt

Grants and funding

This work was supported by the National Natural Science Foundation of China [Grants 81971757 and 81871496], the National Natural Science Youth Foundation of China [Grant 82001975], the Natural Science Youth Foundation of the Jiangsu Province [Grant BK20190841], Zhenjiang Major Project of Social Development in Research and Development [Grant SH2018029], Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application [Grant SS2018003], and Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.