Soy peptide-induced stem cell proliferation: involvement of ERK and TGF-β1.
This study was conducted to investigate the proliferative effect of vegetable soy peptides on adult stem cells (ASCs) in the absence of serum and their possible mechanisms of action. The proliferation of human adipose tissue-derived mesenchymal stem cells (ADSCs) and cord blood-derived mesenchymal stem cells (CB-MSCs) treated with soy peptides was found to increase significantly upon 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Click-iT 5-ethynyl-2'-deoxyuridine flow cytometry assay. In addition, soy peptides led to stepwise phosphorylation of the p44/42 MAPK (ERK), mammalian target of rapamycin (mTOR), p70 S6 kinase, S6 ribosomal protein (S6RP) and eukaryotic initiation factor 4E (eIF4E) in ADSCs. Furthermore, quantitative analysis of the cytokines revealed that the production of transforming growth factor-beta1 (TGF-β1), vascular endothelial growth factor and interleukin-6 increased significantly in response to treatment with soy peptides in both ADSCs and CB-MSCs. Similarly, soy peptide-induced phosphorylation of the ERK/mTOR/S6RP/eIF4E pathway was blocked in response to pretreatment with PD98059, a specific ERK inhibitor. Moreover, inhibition of TGF-β1 through PD98059 pretreatment and a consecutive decrease in ADSC proliferation revealed that TGF-β1 induces the phosphorylation of mTOR/S6RP/eIF4E. Collectively, the results of this study indicate that ERK-dependent production of TGF-β1 plays a crucial role in the soy peptide-induced proliferation of ADSCs under serum-free conditions.
Biospectrum Life Science Institute, Seongnam-Si, Gyunggi-Do, Republic of Korea. jslee@biospectrum.com
Jienny
J
Lee
Kyung-Baeg
KB
Roh
Sang-Cheol
SC
Kim
Jongsung
J
Lee
Deokhoon
D
Park
D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000032:analysis; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D059630:Mesenchymal Stem Cells / Q000473:pathology; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D030262:Soybean Proteins / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D013778:Tetrazolium Salts / Q000032:analysis; D013844:Thiazoles / Q000032:analysis; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D039561:Eukaryotic Initiation Factor-4E; D015850:Interleukin-6; D030262:Soybean Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D048052:Mitogen-Activated Protein Kinase 3; C022616:thiazolyl blue; C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine