Upregulation of BAG3 with apoptotic and autophagic activities in maggot extract‑promoted rat skin wound healing

Mol Med Rep. 2018 Mar;17(3):3807-3812. doi: 10.3892/mmr.2017.8331. Epub 2017 Dec 20.

Abstract

Maggot extract (ME) accelerates rat skin wound healing, however its effect on cell maintenance in wound tissues remains unclear. B‑cell lymphoma (Bcl) 2‑associated athanogene (BAG)3 inhibits apoptosis and promotes autophagy by associating with Bcl‑2 or Beclin 1. Bcl‑2, the downstream effector of signal transducer and activator of transcription 3 signaling, is enhanced in ME‑treated wound tissues, which may reinforce the Bcl‑2 anti‑apoptotic activity and/or cooperate with Beclin 1 to regulate autophagy during wound healing. The present study investigated expression levels of BAG3, Bcl‑2, Beclin 1 and light chain (LC)3 levels in rat skin wound tissues in the presence and absence of ME treatment. The results revealed frequent TUNEL‑negative cell death in the wound tissues in the early three days following injury, irrespective to ME treatment. TUNEL‑positive cells appeared in the wound tissues following 4 days of injury and 150 µg/ml ME efficiently reduced apoptotic rate and enhanced BAG3 and Bcl‑2 expression. Elevated Beclin 1 and LC3 levels and an increased LC3 II ratio were revealed in the ME‑treated tissues during the wound healing. The results of the present study demonstrate the anti‑apoptotic effects of BAG3 and Bcl‑2 in ME‑promoted wound healing. Beclin 1/LC3 mediated autophagy may be favorable in maintaining cell survival in the damaged tissues and ME‑upregulated BAG3 may enhance its activity.

MeSH terms

  • Adaptor Proteins, Signal Transducing / agonists*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / agonists*
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy / drug effects
  • Beclin-1 / genetics
  • Beclin-1 / metabolism
  • Cell Proliferation / drug effects
  • Complex Mixtures / isolation & purification
  • Complex Mixtures / pharmacology*
  • Diptera / chemistry
  • Gene Expression Regulation
  • Larva / chemistry*
  • Male
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Wound Healing / drug effects*
  • Wound Healing / genetics
  • Wounds, Nonpenetrating / genetics
  • Wounds, Nonpenetrating / metabolism
  • Wounds, Nonpenetrating / pathology
  • Wounds, Nonpenetrating / therapy*

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • BAG3 protein, rat
  • Bcl2 protein, rat
  • Beclin-1
  • Becn1 protein, rat
  • Complex Mixtures
  • LC3 protein, rat
  • Microtubule-Associated Proteins
  • Proto-Oncogene Proteins c-bcl-2