N2non-thermal atmospheric pressure plasma promotes wound healing in vitro and in vivo: Potential modulation of adhesion molecules and matrix metalloproteinase-9.
Advances in physics and biology have made it possible to apply non-thermal atmospheric pressure plasma (NTP) in the biomedical field. Although accumulating evidence suggests that NTP has various medicinal effects, such as facilitating skin wound healing on exposed tissue while minimizing undesirable tissue damage, the underlying molecular mechanisms are not fully understood. In this study, NTP generated from N2optimized wound healing in the scratch wound healing assay. In addition, matrix metalloproteinase (MMP)-9 expression and enzyme activity increased and the urokinase-type plasminogen activator (uPA) system was activated after NTP treatment. We also showed that NTP treatment increased Slug and TCF8/ZEB1 expression and decreased that of E-cadherin, suggesting induction of the epithelial-to-mesenchymal transition (EMT). The effect of N2NTP was verified on rat wound model. Taken together, these results suggest that N2NTP promotes wound healing by inducing the EMT and activating the MMP-9/uPA system. These findings show the therapeutic potential of NTP for skin wound healing.
Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
Sung Un
SU
Kang
Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
Jae Won
JW
Choi
Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University College of Medicine, Daejeon, Korea.
Jae Won
JW
Chang
Plasma Technology Research Center, National Fusion Research Institute, Gunsan, Korea.
Kang Il
KI
Kim
Department of otorhinolaryngology, College of Medicine, Konyang University Hospital, Konyang University Myunggok Medical Research Institute, Daejeon, Korea.
Yeon Soo
YS
Kim
Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.|Department of Molecular Science and Technology, Ajou University, Suwon, Korea.
Ju Kyeong
JK
Park
Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.|Department of Molecular Science and Technology, Ajou University, Suwon, Korea.
Yang Eun
YE
Kim
Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
Yun Sang
YS
Lee
Department of Electrical and Computer Engineering, Ajou University, Suwon, Korea.
Sang Sik
SS
Yang
Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.|Department of Molecular Science and Technology, Ajou University, Suwon, Korea.
Chul-Ho
CH
Kim
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D062445:Claudin-1 / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005347:Fibroblasts; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D058626:Plasma Gases / Q000494:pharmacology*; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071250:Snail Family Transcription Factors / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D014950:Wounds, Penetrating / Q000188:drug therapy; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
C568108:CLDN1 protein, human; D015820:Cadherins; D062445:Claudin-1; D058626:Plasma Gases; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C569042:TJP1 protein, human; D014746:Vimentin; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D062826:Zonula Occludens-1 Protein; D014568:Urokinase-Type Plasminogen Activator; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
epithelial-to-mesenchymal transition; matrix metalloproteinase; non-thermal atmospheric pressure plasma; urokinase-type plasminogen activator; wound healing