title: IKVAV regulates ERK1/2 and Akt signalling pathways in BMMSC population growth and proliferation.
abstract: OBJECTIVE
  The molecular mechanism of bone marrow mesenchymal stem cell (BMMSC) population growth and proliferation, induced by Isoleucyl-lysyl-valyl-alanyl-valine (IKVAV), was explored in this study.
  
  
  METHODS
  IKVAV peptides were synthesized by the solid-phase method. Influence of IKVAV on BMMSC population growth and proliferation were investigated by assays of CCK-8, flow cytometry, real-time PCR and western blotting.
  
  
  RESULTS
  IKVAV peptide was found to induce proliferation and proliferating cell nuclear antigen (PCNA) synthesis of BMMSC in a dose- and time-dependent manner. Cell cycle analysis showed that the proportion of IKVAV-treated BMMSC in S phase in was higher than controls. Western blot results suggested that mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signalling pathways were activated by IKVAV by enhancing phosphorylation levels of ERK1/2 and Akt in the BMMSCs. Meanwhile, phosphorylation levels of ERK1/2 and Akt were partially blocked by ERK1/2 inhibitor (PD98059) and Akt inhibitor (wortmannin), respectively.
  
  
  CONCLUSIONS
  Our results demonstrated that IKVAV stimulated BMMSC population growth and proliferation by activating MAPK/ERK1/2 and PI3K/Akt signalling pathways. This study is the first to reveal an enhancement effect of IKVAV peptide on BMMSC at the signal transduction level, and the outcome could provide experimental evidence for application of IKVAV-grafted scaffolds in the field of BMMSC-based tissue engineering.
authors.affiliation: State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, and Biomaterials Science and Engineering Research Center, Wuhan University of Technology, Wuhan, 430070, China.
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.forename: T
authors.initials: T
authors.lastname: Qiu
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Yin
authors.forename: S
authors.initials: S
authors.lastname: Li
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007797:Laminin / Q000737:chemistry / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D005419:Flavonoids; D007797:Laminin; D010446:Peptide Fragments; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin; C083321:isoleucyl-lysyl-valyl-alanyl-valine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one