Wnt7a regulates high autophagic and inflammatory response of epidermis in high-glucose environment

Burns. 2020 Feb;46(1):121-127. doi: 10.1016/j.burns.2019.07.025. Epub 2019 Dec 15.


Type 2 diabetes mellitus (T2DM) is an important reason to cause chronic wound healing or even amputation to patients. A common characteristic of T2DM is the presence of hyperglycemia. Autophagy, a cellular pathway which related to protein and organelle degradation, is relevant to many types of cellular homeostasis change and human diseases including diabetes. However, the relationship between high glucose and autophagy in keratinocytes remains unclear. Previously in our research, wnt7a was proved to accelerate healing process by promoting angiogenesis and ameliorating local inflammation, while little is known about its role in epithelial cells, namely keratinocytes. We hypothesized that reduced expression of wnt7a may contribute to the increment of autophagy. We then compared the expression of autophagic markers such as nlrp3, LC3A/B and bip by high glucose-cultured HaCaT cells, with or without wnt7a treatment. Then we examined the expression levels of TNF-α, TLR-4 and p62 to assess inflammatory statement. High glucose induced a significant increasement in the expression of both autophagic markers and inflammatory markers and these elevated protein levels were reversed after the use of wnt7a. Therefore, these results showed that wnt7a regulates overwhelmed autophagy and inflammation promoted under high glucose condition.

Keywords: Autophagy; Inflammation; Keratinocytes; Wnt7a.

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Autophagy / genetics*
  • Cell Line
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Epidermis / metabolism*
  • Glucose / pharmacology
  • Humans
  • Hyperglycemia / metabolism*
  • Inflammation / metabolism*
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • Microtubule-Associated Proteins / drug effects
  • Microtubule-Associated Proteins / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / drug effects
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Proto-Oncogene Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Toll-Like Receptor 4 / drug effects
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / metabolism
  • Wnt Proteins / metabolism*
  • Wnt Proteins / pharmacology


  • MAP1LC3A protein, human
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Proto-Oncogene Proteins
  • TLR4 protein, human
  • TNF protein, human
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • WNT7A protein, human
  • Wnt Proteins
  • Wnt7a protein, rat
  • Glucose