LIGHT (TNFSF14) Increases the Survival and Proliferation of Human Bone Marrow-Derived Mesenchymal Stem Cells.
LIGHT (HVEM-L, TNFSF14, or CD258), an entity homologous to lymphotoxins, with inducible nature and the ability to compete with herpes simplex virus glycoprotein D for herpes virus entry mediator (HVEM)/tumor necrosis factor (TNF)-related 2, is a member of the TNF superfamily. It is expressed as a homotrimer on activated T cells and dendritic cells (DCs), and has three receptors: HVEM, LT-β receptor (LTβR), and decoy receptor 3 (DcR3). So far, three receptors with distinct cellular expression patterns are known to interact with LIGHT. Follicular DCs and stromal cells bind LIGHT through LTβR. We monitored the effects of LIGHT on human bone marrow-derived mesenchymal stem cells (BM-MSCs). At first, we checked the negative and positive differentiation markers of BM-MSCs. And we confirmed the quality of MSCs by staining cells undergoing adipogenesis (Oil Red O staining), chondrogenesis (Alcian blue staining), and osteogenesis (Alizarin red staining). After rhLIGHT treatment, we monitored the count, viability, and proliferation of cells and cell cycle distribution. PDGF and TGFβ production by rhLIGHT was examined by ELISA, and the underlying biological mechanisms were studied by immunoblotting by rhLIGHT treatment. LTβR was constitutively expressed on the surface of human BM-MSCs. Cell number and viability increased after rhLIGHT treatment. BM-MSC proliferation was induced by an increase in the S/G2/M phase. The expression of not only diverse cyclins such as cyclin B1, D1, D3, and E, but also CDK1 and CDK2, increased, while that of p27 decreased, after rhLIGHT treatment. RhLIGHT-induced PDGF and TGFβ production mediated by STAT3 and Smad3 activation accelerated BM-MSC proliferation. Thus, LIGHT and LTβR interaction increases the survival and proliferation of human BM-MSCs, and therefore, LIGHT might play an important role in stem cell therapy.
Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Republic of Korea.
Sook-Kyoung
SK
Heo
Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Republic of Korea.
Eui-Kyu
EK
Noh
Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Republic of Korea.
Gi-Dong
GD
Gwon
Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Republic of Korea.
Jeong Yi
JY
Kim
Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Republic of Korea.
Jae-Cheol
JC
Jo
Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Republic of Korea.
Yunsuk
Y
Choi
Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Republic of Korea.
SuJin
S
Koh
Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Republic of Korea.
Jin Ho
JH
Baek
Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Republic of Korea.
Young Joo
YJ
Min
Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-060, Republic of Korea.|Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 682-714, Republic of Korea.
Hawk
H
Kim
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016203:CDC2 Protein Kinase; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D053259:Lymphotoxin beta Receptor / Q000235:genetics* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D046228:Microarray Analysis; D010011:Osteocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D016213:Cyclins; C505697:LTBR protein, human; D053259:Lymphotoxin beta Receptor; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; C497790:SMAD3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051900:Smad3 Protein; C505914:TNFSF14 protein, human; D016212:Transforming Growth Factor beta; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; C075278:platelet-derived growth factor A; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases