title: Role of thioredoxin 1 and thioredoxin 2 on proliferation of human adipose tissue-derived mesenchymal stem cells.
abstract: Thioredoxin (TRX) is a ubiquitous redox protein that is involved in numerous biological functions, including the first unique step in DNA synthesis. TRX provides control over a number of transcription factors affecting cell proliferation and death through a mechanism referred to as redox regulation. In mammals, there are at least 3 members of the TRX family: TRX1, TRX2, and sperm TRX. To investigate the role of TRX1 and TRX2 in human adipose tissue-derived mesenchymal stem cells (hADSC), we modulated TRX1 and TRX2 expressions in hADSC using a lentiviral gene transfer system and small interfering RNA technique. Reverse transcription-polymerase chain reaction analysis confirmed the changes in expression of TRX1 and TRX2 in lentivirus-transduced or small interfering RNA-transfected cells. Although overexpression of TRX1 and TRX2 did not affect the differentiation of hADSC into adipogenic and osteogenic lineages, it increased the proliferation of hADSC compared with control lentivirus-transduced cells, decreased reactive oxygen species production, and inhibited oxidant-induced cell death. Downregulation of TRX1 and TRX2 inhibited cell proliferation. The treatment of U0126 blocked TRX-induced increase in cell proliferation. Overexpression of TRX1 and TRX2 increased ERK1/2 phosphorylation, nuclear factor-kappaB activation, and β-catenin/Tcf promoter activities and inhibited lucine zipper tumor suppressor 2 expression. On the contrary, downregulation of TRX1 and TRX2 expression induced inhibition of ERK1/2 phosphorylation, nuclear factor-kappaB activation, and β-catenin/Tcf promoter activities and increased lucine zipper tumor suppressor 2 expression. Activation of Wnt signal increased ERK1/2 activities in hADSC. These results indicated that TRX1 and TRX2 regulate the proliferation and survival of hADSC; these processes are mediated by the activation of ERK1/2.
authors.affiliation: Department of Physiology, School of Medicine, Pusan National University, Yangsan, Korea.
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Song
authors.forename: Hyun Hwa
authors.initials: HH
authors.lastname: Cho
authors.forename: Byung-Joo
authors.initials: BJ
authors.lastname: Lee
authors.forename: Yong Chan
authors.initials: YC
authors.lastname: Bae
authors.forename: Jin Sup
authors.initials: JS
authors.lastname: Jung
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002070:Butadienes; D024101:Mitochondrial Proteins; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; C467002:TXN2 protein, human; C113580:U 0126; D013879:Thioredoxins; D048049:Extracellular Signal-Regulated MAP Kinases