KEGG   PATHWAY: mfot05323
Entry
mfot05323                   Pathway                                
Name
Rheumatoid arthritis - Microtus fortis (reed vole)
Description
Rheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune system elevates pro-inflammatory cytokines and chemokines levels, which can promote synovial angiogenesis and leukocyte infiltration. The synovium forms a hyperplastic pannus with infiltrated macrophage-like and fibroblast-like synoviocytes and invades joints by secreting proteinases and inducing osteoclast differentiation.
Class
Human Diseases; Immune disease
Pathway map
mfot05323  Rheumatoid arthritis
mfot05323

Organism
Microtus fortis (reed vole) [GN:mfot]
Gene
126505596  T-lymphocyte activation antigen CD80 [KO:K05412]
126488737  T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
126508842  T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470]
126508824  cytotoxic T-lymphocyte protein 4 isoform X1 [KO:K06538]
126499777  class II histocompatibility antigen, M alpha chain [KO:K06752]
126499785  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
126499788  HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752]
126499795  RLA class II histocompatibility antigen, DP alpha-1 chain [KO:K06752]
126500662  rano class II histocompatibility antigen, B-1 beta chain-like [KO:K06752]
126494845  rano class II histocompatibility antigen, A beta chain-like [KO:K06752]
126494850  H-2 class II histocompatibility antigen, E-D beta chain-like isoform X1 [KO:K06752]
126494852  H-2 class II histocompatibility antigen, E-U alpha chain [KO:K06752]
126494853  HLA class II histocompatibility antigen, DO beta chain-like [KO:K06752]
126494854  rano class II histocompatibility antigen, B-1 beta chain-like isoform X1 [KO:K06752]
126494856  H-2 class II histocompatibility antigen, A-R alpha chain-like [KO:K06752]
126494857  H-2 class II histocompatibility antigen, A-F alpha chain-like [KO:K06752]
126494858  HLA class II histocompatibility antigen, DR beta 5 chain-like [KO:K06752]
126495602  rano class II histocompatibility antigen, A beta chain [KO:K06752]
126495603  H-2 class II histocompatibility antigen, A-F alpha chain-like [KO:K06752]
126495604  H-2 class II histocompatibility antigen, A-R alpha chain-like [KO:K06752]
126502560  HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752]
126502685  class II histocompatibility antigen, M beta 1 chain [KO:K06752]
126496141  rano class II histocompatibility antigen, A beta chain-like [KO:K06752]
126493857  uncharacterized protein LOC126493857 [KO:K10784]
126515909  integrin alpha-L [KO:K05718]
126513667  integrin beta-2-like protein [KO:K06464]
126502148  integrin beta-2 [KO:K06464]
126490552  intercellular adhesion molecule 1 isoform X1 [KO:K06490]
126513255  interleukin-15 isoform X1 [KO:K05433]
126513937  tumor necrosis factor ligand superfamily member 13 isoform X1 [KO:K05475]
126498327  tumor necrosis factor ligand superfamily member 13B isoform X1 [KO:K05476]
126494876  lymphotoxin-beta isoform X1 [KO:K03157]
126494877  tumor necrosis factor [KO:K03156]
126496717  interleukin-1 alpha isoform X1 [KO:K04383]
126496850  interleukin-1 beta [KO:K04519]
126491159  interleukin-6 [KO:K05405]
126493667  interleukin-11 isoform X1 [KO:K05417]
126509990  interleukin-18 [KO:K05482]
126511616  toll-like receptor 2 [KO:K10159]
126507954  toll-like receptor 4 [KO:K10160]
126497948  transcription factor Jun [KO:K04448]
126515189  protein c-Fos [KO:K04379]
126494578  transforming growth factor beta-1 proprotein [KO:K13375]
126505361  transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
126507732  transforming growth factor beta-3 proprotein [KO:K13377]
126492059  interleukin-23 subunit alpha isoform X1 [KO:K05426]
126489678  interleukin-17A [KO:K05489]
126487575  parathyroid hormone [KO:K05261]
126491876  macrophage colony-stimulating factor 1 isoform X1 [KO:K05453]
126487114  tumor necrosis factor receptor superfamily member 11A [KO:K05147]
126505670  V-type proton ATPase catalytic subunit A [KO:K02145] [EC:7.1.2.2]
126515605  V-type proton ATPase subunit B, kidney isoform [KO:K02147]
126491323  V-type proton ATPase subunit B, brain isoform [KO:K02147]
126513479  V-type proton ATPase subunit C 1 [KO:K02148]
126501336  V-type proton ATPase subunit C 2 isoform X1 [KO:K02148]
126511364  V-type proton ATPase subunit D [KO:K02149]
126514824  V-type proton ATPase subunit E 1 [KO:K02150]
126504134  V-type proton ATPase subunit E 2 [KO:K02150]
126512998  V-type proton ATPase subunit F-like [KO:K02151]
126501175  V-type proton ATPase subunit F [KO:K02151]
126507332  V-type proton ATPase subunit G 3 [KO:K02152]
126488378  V-type proton ATPase subunit G 1 [KO:K02152]
126494882  V-type proton ATPase subunit G 2 isoform X1 [KO:K02152]
126487200  V-type proton ATPase subunit e 2 [KO:K02153]
126496903  V-type proton ATPase subunit e 1 isoform X1 [KO:K02153]
126510301  V-type proton ATPase 116 kDa subunit a 1 isoform X1 [KO:K02154]
126504303  V-type proton ATPase 116 kDa subunit a 2 isoform X1 [KO:K02154]
126498188  V-type proton ATPase 116 kDa subunit a 3 [KO:K02154]
126505211  V-type proton ATPase 116 kDa subunit a 4 [KO:K02154]
126502654  V-type proton ATPase subunit d 1 [KO:K02146]
126516099  V-type proton ATPase subunit d 2 [KO:K02146]
126515563  V-type proton ATPase subunit H isoform X1 [KO:K02144]
126490265  V-type proton ATPase subunit S1 [KO:K03662]
126497885  V-type proton ATPase 16 kDa proteolipid subunit c [KO:K02155]
126513167  V-type proton ATPase 21 kDa proteolipid subunit c'' [KO:K03661]
126489972  cathepsin K isoform X1 [KO:K01371] [EC:3.4.22.38]
126490565  LOW QUALITY PROTEIN: tartrate-resistant acid phosphatase type 5 [KO:K14379] [EC:3.1.3.2]
126493288  LOW QUALITY PROTEIN: stromelysin-1-like [KO:K01394] [EC:3.4.24.17]
126502700  procathepsin L [KO:K01365] [EC:3.4.22.15]
126510957  granulocyte-macrophage colony-stimulating factor [KO:K05427]
126494814  C-C motif chemokine 5 [KO:K12499]
126492357  C-C motif chemokine 2-like isoform X1 [KO:K14624]
126492360  C-C motif chemokine 12-like [KO:K14624]
126494823  C-C motif chemokine 3-like isoform X1 [KO:K05408]
126508749  C-C motif chemokine 20 isoform X1 [KO:K14625]
126506338  C-X-C motif chemokine 3-like [KO:K05505]
126506591  C-X-C motif chemokine 2-like [KO:K05505]
126506592  growth-regulated alpha protein [KO:K05505]
126506339  alveolar macrophage chemotactic factor-like [KO:K05506]
126505459  stromal cell-derived factor 1 isoform X1 [KO:K10031]
126488914  vascular endothelial growth factor A isoform X1 [KO:K05448]
126513474  vascular endothelial growth factor receptor 1 isoform X1 [KO:K05096] [EC:2.7.10.1]
126514397  angiopoietin-1 isoform X1 [KO:K05465]
126497972  angiopoietin-1 receptor isoform X1 [KO:K05121] [EC:2.7.10.1]
126515663  interferon gamma [KO:K04687]
Compound
C00080  H+
C00584  Prostaglandin E2
C05443  Vitamin D3
Reference
PMID:16127012
  Authors
Zwerina J, Redlich K, Schett G, Smolen JS
  Title
Pathogenesis of rheumatoid arthritis: targeting cytokines.
  Journal
Ann N Y Acad Sci 1051:716-29 (2005)
DOI:10.1196/annals.1361.116
Reference
PMID:20036936
  Authors
Szekanecz Z, Vegvari A, Szabo Z, Koch AE
  Title
Chemokines and chemokine receptors in arthritis.
  Journal
Front Biosci (Schol Ed) 2:153-67 (2010)
DOI:10.2741/53
Reference
PMID:20651747
  Authors
Isaacs JD
  Title
The changing face of rheumatoid arthritis: sustained remission for all?
  Journal
Nat Rev Immunol 10:605-11 (2010)
DOI:10.1038/nri2804
Reference
PMID:17195034
  Authors
Strand V, Kimberly R, Isaacs JD
  Title
Biologic therapies in rheumatology: lessons learned, future directions.
  Journal
Nat Rev Drug Discov 6:75-92 (2007)
DOI:10.1038/nrd2196
Reference
PMID:20193003
  Authors
Bartok B, Firestein GS
  Title
Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis.
  Journal
Immunol Rev 233:233-55 (2010)
DOI:10.1111/j.0105-2896.2009.00859.x
Reference
PMID:17502360
  Authors
Dai SM, Shan ZZ, Xu H, Nishioka K
  Title
Cellular targets of interleukin-18 in rheumatoid arthritis.
  Journal
Ann Rheum Dis 66:1411-8 (2007)
DOI:10.1136/ard.2006.067793
Reference
PMID:9627005
  Authors
Koch AE
  Title
Review: angiogenesis: implications for rheumatoid arthritis.
  Journal
Arthritis Rheum 41:951-62 (1998)
DOI:10.1002/1529-0131(199806)41:6<951::AID-ART2>3.0.CO;2-D
Reference
PMID:20305562
  Authors
Szekanecz Z, Besenyei T, Szentpetery A, Koch AE
  Title
Angiogenesis and vasculogenesis in rheumatoid arthritis.
  Journal
Curr Opin Rheumatol 22:299-306 (2010)
DOI:10.1097/BOR.0b013e328337c95a
Reference
PMID:15059264
  Authors
Brunner-Weinzierl MC, Hoff H, Burmester GR
  Title
Multiple functions for CD28 and cytotoxic T lymphocyte antigen-4 during different phases of T cell responses: implications for arthritis and autoimmune diseases.
  Journal
Arthritis Res Ther 6:45-54 (2004)
DOI:10.1186/ar1158
Reference
PMID:11861618
  Authors
Theill LE, Boyle WJ, Penninger JM
  Title
RANK-L and RANK: T cells, bone loss, and mammalian evolution.
  Journal
Annu Rev Immunol 20:795-823 (2002)
DOI:10.1146/annurev.immunol.20.100301.064753
Reference
PMID:19184540
  Authors
Mensah KA, Li J, Schwarz EM
  Title
The emerging field of osteoimmunology.
  Journal
Immunol Res 45:100-13 (2009)
DOI:10.1007/s12026-009-8093-x
Reference
PMID:16313349
  Authors
Takayanagi H, Sato K, Takaoka A, Taniguchi T
  Title
Interplay between interferon and other cytokine systems in bone metabolism.
  Journal
Immunol Rev 208:181-93 (2005)
DOI:10.1111/j.0105-2896.2005.00337.x
Reference
PMID:20392226
  Authors
Takayanagi H
  Title
New immune connections in osteoclast formation.
  Journal
Ann N Y Acad Sci 1192:117-23 (2010)
DOI:10.1111/j.1749-6632.2009.05303.x
Reference
PMID:19585227
  Authors
Nakashima T, Takayanagi H
  Title
Osteoimmunology: crosstalk between the immune and bone systems.
  Journal
J Clin Immunol 29:555-67 (2009)
DOI:10.1007/s10875-009-9316-6
Reference
PMID:19455385
  Authors
Nakashima T, Takayanagi H
  Title
Osteoclasts and the immune system.
  Journal
J Bone Miner Metab 27:519-29 (2009)
DOI:10.1007/s00774-009-0089-z
Reference
PMID:17380158
  Authors
Takayanagi H
  Title
Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems.
  Journal
Nat Rev Immunol 7:292-304 (2007)
DOI:10.1038/nri2062
Reference
PMID:20510236
  Authors
Fox DA, Gizinski A, Morgan R, Lundy SK
  Title
Cell-cell interactions in rheumatoid arthritis synovium.
  Journal
Rheum Dis Clin North Am 36:311-23 (2010)
DOI:10.1016/j.rdc.2010.02.004
Reference
PMID:15055519
  Authors
Rho J, Takami M, Choi Y
  Title
Osteoimmunology: interactions of the immune and skeletal systems.
  Journal
Mol Cells 17:1-9 (2004)
Related
pathway
mfot04370  VEGF signaling pathway
mfot04380  Osteoclast differentiation
mfot04620  Toll-like receptor signaling pathway
mfot04659  Th17 cell differentiation
mfot04660  T cell receptor signaling pathway
mfot04670  Leukocyte transendothelial migration
KO pathway
ko05323   
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