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

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 a ct iv it y.