PMID- 35292250 OWN - NLM STAT- MEDLINE DCOM- 20220407 LR - 20220407 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 921 DP - 2022 Apr 15 TI - Peptides derived from sea cucumber accelerate cells proliferation and migration for wound healing by promoting energy metabolism and upregulating the ERK/AKT pathway. PG - 174885 LID - S0014-2999(22)00146-7 [pii] LID - 10.1016/j.ejphar.2022.174885 [doi] AB - Numerous bioactive peptides have high potential in accelerating skin repair. This study aimed to explore wound healing capacity of sea cucumber-derived tetrapeptides with amino acid sequence of Val-Thr-Pro-Tyr (VTPY) and Val-Leu-Leu-Tyr (VLLY) by human skin fibroblast (HSF) and human umbilical vein endothelial cells (HUVEC) in vitro. The results showed that VTPY and VLLY possessed excellent capacity to induce the proliferation and migration of HSF cells and HUVEC cells. Among them, VTPY possessed a higher cell migration-promotion capacity than VLLY. Meanwhile, VTPY and VLLY increased mitochondrial respiratory capacity of cells, leading to the significant increase in adenosine triphosphate (ATP) production. Additionally, VTPY and VLLY significantly increased the percentage of S phase in cell cycle of HUVEC via upregulation of extracellular regulated protein kinases (ERK) and protein kinase B (AKT) signaling pathway. Molecular docking further indicated the interaction of peptides with mitogen-activated protein kinase phosphatase (MKP) and PH domain leucine-rich repeat protein phosphatase (PHLPP) binding site in the ERK2 and AKT, respectively, leading to subsequent increased phosphorylation of ERK1/2 and AKT. Overall, peptides of VTPY and VLLY possessed outstanding capacity to induce the proliferation and migration of HSF cells and HUVEC cells in vitro and the mechanism was mainly related to improving mitochondrial respiratory capacity to produce more ATP for biological energy, blocking the binding of MKP to ERK2 and PHLPP to AKT and thus upregulating the ERK/AKT pathway. CI - Copyright (c) 2022. Published by Elsevier B.V. FAU - Zheng, Zhihong AU - Zheng Z AD - National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, PR China. FAU - Li, Mengqi AU - Li M AD - National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, PR China. FAU - Jiang, Pengfei AU - Jiang P AD - National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, PR China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, PR China. FAU - Sun, Na AU - Sun N AD - National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, PR China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, PR China. Electronic address: sunna1215@126.com. FAU - Lin, Songyi AU - Lin S AD - National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, PR China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian, 116034, PR China. Electronic address: linsongyi730@163.com. LA - eng PT - Journal Article DEP - 20220312 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Peptides) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Cell Proliferation MH - Energy Metabolism MH - Human Umbilical Vein Endothelial Cells/metabolism MH - Humans MH - Molecular Docking Simulation MH - Peptides/metabolism/pharmacology MH - *Proto-Oncogene Proteins c-akt/metabolism MH - *Sea Cucumbers/metabolism MH - Wound Healing OTO - NOTNLM OT - Energy metabolism OT - HSF cells OT - HUVEC cells OT - Molecular docking OT - Sea cucumber derived peptide OT - Wound healing EDAT- 2022/03/17 06:00 MHDA- 2022/04/08 06:00 CRDT- 2022/03/16 05:42 PHST- 2021/10/08 00:00 [received] PHST- 2022/03/03 00:00 [revised] PHST- 2022/03/09 00:00 [accepted] PHST- 2022/03/17 06:00 [pubmed] PHST- 2022/04/08 06:00 [medline] PHST- 2022/03/16 05:42 [entrez] AID - S0014-2999(22)00146-7 [pii] AID - 10.1016/j.ejphar.2022.174885 [doi] PST - ppublish SO - Eur J Pharmacol. 2022 Apr 15;921:174885. doi: 10.1016/j.ejphar.2022.174885. Epub 2022 Mar 12.