PMID- 24811302 OWN - NLM STAT- MEDLINE DCOM- 20150313 LR - 20220318 IS - 1724-6040 (Electronic) IS - 0391-3988 (Linking) VI - 37 IP - 5 DP - 2014 May TI - Alpinia oxyphylla Miquel fruit extract activates MAPK-mediated signaling of PAs and MMP2/9 to induce Schwann cell migration and nerve regeneration. PG - 402-13 LID - 10.5301/ijao.5000313 [doi] AB - OBJECTIVES: 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. FAU - Chang, Yung-Ming AU - Chang YM AD - 2 Chinese Medicine Department, E-DA Hospital, Kaohsiung - Taiwan. FAU - Ye, Chi-Xin AU - Ye CX FAU - Ho, Tsung-Jung AU - Ho TJ FAU - Tsai, Te-Neng AU - Tsai TN FAU - Chiu, Ping-Ling AU - Chiu PL FAU - Tsai, Chin-Chuan AU - Tsai CC FAU - Lin, Yueh-Min AU - Lin YM FAU - Kuo, Chia-Hua AU - Kuo CH FAU - Tsai, Fuu-Jen AU - Tsai FJ FAU - Tsai, Chang-Hai AU - Tsai CH FAU - Huang, Chih-Yang AU - Huang CY LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140417 PL - United States TA - Int J Artif Organs JT - The International journal of artificial organs JID - 7802649 RN - 0 (Alpinia oxyphylla fruit extract) RN - 0 (Plant Extracts) RN - EC 3.4.21.68 (Tissue Plasminogen Activator) RN - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - *Alpinia MH - Animals MH - Cell Movement/*drug effects/physiology MH - MAP Kinase Signaling System/*drug effects/physiology MH - Matrix Metalloproteinase 2/metabolism MH - Matrix Metalloproteinase 9/metabolism MH - Nerve Regeneration/*drug effects/physiology MH - Plant Extracts/*pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Schwann Cells/*drug effects/metabolism MH - Tissue Plasminogen Activator/metabolism MH - Urokinase-Type Plasminogen Activator/metabolism EDAT- 2014/05/09 06:00 MHDA- 2015/03/17 06:00 CRDT- 2014/05/10 06:00 PHST- 2014/02/01 00:00 [accepted] PHST- 2014/05/10 06:00 [entrez] PHST- 2014/05/09 06:00 [pubmed] PHST- 2015/03/17 06:00 [medline] AID - B89294D2-96D8-413E-992F-20547AA8944B [pii] AID - 10.5301/ijao.5000313 [doi] PST - ppublish SO - Int J Artif Organs. 2014 May;37(5):402-13. doi: 10.5301/ijao.5000313. Epub 2014 Apr 17.