IKVAV regulates ERK1/2 and Akt signalling pathways in BMMSC population growth and proliferation

Abstract

ObjectivesThe 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.Materials and methodsIKVAV 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.ResultsIKVAV 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.ConclusionsOur 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.

Ile‐Lys‐Val‐ala‐Val (IKVAV) peptide for neuronal tissue engineering

“…Ile‐Lys‐Val‐ala‐Val directly participates in signaling pathways and enhances bone marrow mesenchymal stem cell (BMMSC) proliferation. The IKVAV peptide directly attaches to the cell membrane and activates the mitogen‐activated protein kinase/extracellular signal‐regulated kinase and phosphatidylinositol 3‐kinase/protein kinase B (PI3K/Akt) signaling pathways . The IKVAV epitope is mediated through the β1 integrin receptor, and with the increase in β1 integrin signaling, it suppress astroglysis in ependymal cells .…”

“…The IKVAV peptide directly attaches to the cell membrane and activates the mitogen-activated protein kinase/extracellular signalregulated kinase and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathways. 16 The IKVAV epitope is mediated through the β1 integrin receptor, 17 and with the increase in β1 integrin signaling, it suppress astroglysis in ependymal cells. 18 Dorsal root ganglion (DRG) cells were directed along a path of bound IKVAV peptide onto the middle of a gradient of the peptide.…”

Low‐intensity pulsed ultrasound activates ERK1/2 and PI3K‐Akt signalling pathways and promotes the proliferation of human amnion‐derived mesenchymal stem cells

“…Extracellular signal-regulated kinases (ERK1/2) and PI3K-Akt signalling pathways have been reported to play an important role in cell proliferation. 25,49 Western blot was performed to monitor the key proteins of the ERK1/2 and PI3K-Akt signalling pathways. It was found that significant phosphorylation of ERK1/2 and Akt was rapidly induced by LIPUS ( Figure 6A…”

“…Phosphorylated Akt acts on the downstream target factors and plays a role in cell cycle regulation and cell growth. It has been reported that PI3K‐Akt pathway serves an important role in the proliferation of MSCs . However, whether ERK1/2 and PI3K/Akt signalling pathways are involved in the effect of LIPUS on proliferation of hAD‐MSCs are unknown.…”

PRGD/PDLLA conduit potentiates rat sciatic nerve regeneration and the underlying molecular mechanism

“…The new regenerated nerves on 7 and 35 days postimplantation were collected for RNA expression analysis followed by our previous work [23]. Briefly, total RNA was isolated using Trizol reagent (Invitrogen, Carlsbad, USA) and was reverse transcribed into cDNA.…”