title: Alpinia oxyphylla Miquel fruit extract activates MAPK-mediated signaling of PAs and MMP2/9 to induce Schwann cell migration and nerve regeneration.
abstract: OBJECTIVE
  This study investigates the molecular mechanisms by which Alpiniae oxyphyllae fructus (AOF) promotes neuron regeneration.
  
  
  METHODS
  A piece of silicone rubber was guided across a 15 mm gap in the sciatic nerve of a rat. This nerve gap was then filled with different concentrations of AOF extract (0-200 mg/ml). We investigated the role of MAPK (ERK1/2, JNK and p38) pathways for AOF-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production in RSC96 Schwann cells.
  
  
  RESULTS
  The results showed that AOF increased the expressions of uPA, tPA, MMP-9, and MAPKs in vivo. In vitro, our results show that treatment with AOF extract induces ERK1/2, JNK, and p38 phosphorylation to activate the downstream PAs and MMPs signaling expression. AOF-stimulated ERK1/2, JNK, and p38 phosphorylation attenuated by individual pretreatment with siRNAs or inhibitors (U0126, SP600125 and SB203580), resulting in migration and uPA-related signal pathway inhibition.
  
  
  CONCLUSIONS
  Taken together our data suggests the MAPKs (ERK1/2, JNK and p38), PAs (uPA, tPA), MMP (MMP2, MMP9) regenerative and migration signaling pathway of Schwann cells regulated by AOF extract might play a major role in Schwann cell migration and damaged peripheral nerve regeneration.
authors.affiliation: 2 Chinese Medicine Department, E-DA Hospital, Kaohsiung - Taiwan.
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Chang
authors.forename: Chi-Xin
authors.initials: CX
authors.lastname: Ye
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.forename: Te-Neng
authors.initials: TN
authors.lastname: Tsai
authors.forename: Ping-Ling
authors.initials: PL
authors.lastname: Chiu
authors.forename: Chin-Chuan
authors.initials: CC
authors.lastname: Tsai
authors.forename: Yueh-Min
authors.initials: YM
authors.lastname: Lin
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Kuo
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D032429:Alpinia; D000818:Animals; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000187:drug effects* / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: C442779:Alpinia oxyphylla fruit extract; D010936:Plant Extracts; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9