Oncostatin M induces proliferation of human adipose tissue-derived mesenchymal stem cells.
Interleukin-6 (IL-6) subfamily of cytokines, including oncostatin M (OSM), leukemia inhibitory factor (LIF), and IL-6, has been implicated in a variety of physiological responses, such as cell growth, differentiation, and inflammation. In the present study, we demonstrated that both OSM and LIF stimulated the proliferation of human adipose tissue-derived mesenchymal stem cells (hATSCs), however, IL-6 had no effect on cell proliferation. OSM treatment induced phosphorylation of ERK, and pretreatment with U0126, a MEK inhibitor, prevented the OSM-stimulated proliferation of hATSCs, suggesting that the MEK/ERK pathway is involved in the OSM-induced proliferation. Treatment with OSM also induced phosphorylation of JAK2 and JAK3, and pretreatment of the cells with WHI-P131, a JAK3 inhibitor, but not with AG490, a JAK2 inhibitor, attenuated the OSM-induced proliferation of hATSCs. Furthermore, OSM treatment elicited phosphorylation of STAT1 and STAT3, and pretreatment with WHI-P131 specifically prevented the OSM-induced phosphorylation of STAT1, without affecting the OSM-induced phosphorylation of ERK and STAT3. These results suggest that two separate signaling pathways, such as MEK/ERK and JAK3/STAT1, are independently involved in the OSM-stimulated proliferation of hATSCs.
Song
Hae Young
HY
Department of Physiology and The Medical Research Institute, College of Medicine, Pusan National University, Busan 602-739, Republic of Korea.
Jeon
Eun Su
ES
Jung
Jin Sup
JS
Kim
Jae Ho
JH
D000273:Adipose Tissue / Q000166:cytology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002070:Butadienes / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D053616:Janus Kinase 3; D053605:Leukemia Inhibitory Factor; D020935:MAP Kinase Signaling System / Q000502:physiology; D008648:Mesoderm / Q000166:cytology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
D000970:Antineoplastic Agents; D002070:Butadienes; D004791:Enzyme Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D009570:Nitriles; C508351:OSM protein, human; D010455:Peptides; C113580:U 0126; D053683:Oncostatin M; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases