|  Help  |  About  |  Contact Us

Publication : Regulation of the Cell Cycle and Inflammatory Arthritis by the Transcription Cofactor <i>LBH</i> Gene.

First Author  Matsuda S Year  2017
Journal  J Immunol Volume  199
Issue  7 Pages  2316-2322
PubMed ID  28807995 Mgi Jnum  J:250898
Mgi Id  MGI:6103637 Doi  10.4049/jimmunol.1700719
Citation  Matsuda S, et al. (2017) Regulation of the Cell Cycle and Inflammatory Arthritis by the Transcription Cofactor LBH Gene. J Immunol 199(7):2316-2322
abstractText  Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) display unique aggressive behavior, invading the articular cartilage and promoting inflammation. Using an integrative analysis of RA risk alleles, the transcriptome and methylome in RA FLS, we recently identified the limb bud and heart development (LBH) gene as a key dysregulated gene in RA and other autoimmune diseases. Although some evidence suggests that LBH could modulate the cell cycle, the precise mechanism is unknown and its impact on inflammation in vivo has not been defined. Our cell cycle analysis studies show that LBH deficiency in FLS leads to S-phase arrest and failure to progress through the cell cycle. LBH-deficient FLS had increased DNA damage and reduced expression of the catalytic subunit of DNA polymerase alpha. Decreased DNA polymerase alpha was followed by checkpoint arrest due to phosphorylation of checkpoint kinase 1. Because DNA fragments can increase arthritis severity in preclinical models, we then explored the effect of LBH deficiency in the K/BxN serum transfer model. Lbh knockout exacerbated disease severity, which is associated with elevated levels of IL-1beta and checkpoint kinase 1 phosphorylation. These studies indicate that LBH deficiency induces S-phase arrest that, in turn, exacerbates inflammation. Because LBH gene variants are associated with type I diabetes mellitus, systemic lupus erythematosus, RA, and celiac disease, these results suggest a general mechanism that could contribute to immune-mediated diseases.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

7 Bio Entities

0 Expression