Connexin 43 upregulation in burns promotes burn conversion through spread of apoptotic death signals

Burns. 2020 Sep;46(6):1389-1397. doi: 10.1016/j.burns.2020.03.011. Epub 2020 Apr 30.

Abstract

Background: Burn wounds continue to worsen after initial injury in a process known as burn conversion, which lasts about 3-5 days. It causes burn wounds to enlarge and deepen, leading to greater morbidity. Apoptosis is one of the factors contributing to the conversion of the zone of stasis into the zone of coagulation. Suppression of apoptosis has been associated with reducing burn conversion. Connexin 43 (Cx43) gap junctions facilitate the spread of apoptotic signals from dying cells to healthy neighbouring cells in injured tissues through the bystander effect.

Objectives: The study is to understand the role of Cx43 in burn conversion.

Methods: In our study, 15 burn tissue samples were arranged into three groups as early (beginning of burn conversion), intermediate (extensive burn conversion) and late (established burn conversion) burns.

Results: We found a striking increase in the amount of Cx43 protein expressed in the dermal fibroblasts (identified with heat shock protein 47 (HSP47) staining) in the zone of stasis in early and intermediate burns. These dermal fibroblasts also express high levels of cleaved-Caspase 3 indicating on-going apoptosis.

Conclusions: Our findings suggest that elevation of Cx43 may play an active role in burn conversion spreading apoptosis in the early and intermediate burn wound.

Keywords: Apoptosis; Burn; Cell death; Connexin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis*
  • Burns / metabolism*
  • Burns / pathology
  • Bystander Effect*
  • Caspase 3 / metabolism
  • Connexin 43 / metabolism*
  • Dermis / metabolism*
  • Dermis / pathology
  • Disease Progression
  • Female
  • Fibroblasts / metabolism*
  • Gap Junctions / metabolism
  • HSP47 Heat-Shock Proteins / metabolism
  • Humans
  • Male
  • Middle Aged

Substances

  • Connexin 43
  • GJA1 protein, human
  • HSP47 Heat-Shock Proteins
  • SERPINH1 protein, human
  • CASP3 protein, human
  • Caspase 3