FLIP and MAPK play crucial roles in the MLN51-mediated hyperproliferation of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis.
One of the characteristic features of the pathogenesis of rheumatoid arthritis is synovial hyperplasia. We have reported previously that metastatic lymph node 51 (MLN51) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are involved in the proliferation of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis. In this study, we have found that: (1) GM-CSF-mediated MLN51 upregulation is attributable to both transcriptional and post-translational control in rheumatoid arthritis fibroblast-like synoviocytes; (2) p38 mitogen-activated protein kinase plays a key role in the upregulation of MLN51; and (3) FLICE-inhibitory protein is upregulated downstream of MLN51 in response to GM-CSF, resulting in the proliferation of fibroblast-like synoviocytes. These results imply that GM-CSF signaling activates mitogen-activated protein kinase, followed by the upregulation of MLN51 and FLICE-inhibitory protein, resulting in fibroblast-like synoviocyte hyperplasia in rheumatoid arthritis.
Ha
Ju-Eun
JE
Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-Do, South Korea.
Choi
Young-Eun
YE
Jang
Jinah
J
Yoon
Cheol-Hee
CH
Kim
Ho-Youn
HY
Bae
Yong-Soo
YS
D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000096:biosynthesis / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016601:RNA-Binding Proteins; D013583:Synovial Membrane / Q000166:cytology*; D015854:Up-Regulation
C459802:CASC3 protein, human; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020928:Mitogen-Activated Protein Kinases