Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.17 (
MMP-3
)
3,419
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We previously reported that
follistatin-related protein
(
FRP
)/TSC-36 was one of the target antigens of autoantibodies in rheumatoid arthritis (RA) and that the appearance of serum autoantibodies to
FRP
correlated to disease activity in RA. However, the significance of
FRP
in autoimmunity remained to be explained due to the unknown function of
FRP
. Here, we disclose in part the function of
FRP
. Transforming growth factor (TGF)-beta augmented
FRP
gene expression in synovial cells.
FRP
reduced synovial production of matrix metalloproteinase (MMP)-1,
MMP-3
and prostaglandin E(2), potent agonists of joint destruction in RA. In contrast, autoantibodies to
FRP
from patients with RA increased their production by blocking
FRP
activity, probably in the autocrine system. Moreover,
FRP
down-regulated synovial expression of FOS (c-fos), which seemed responsible for the reduction in MMP-1 and
MMP-3
caused by
FRP
. Therefore,
FRP
and its autoantibody can be regarded as defensive and offensive factors respectively in rheumatoid arthropathy. The major epitope of autoantibodies to
FRP
was mapped to the sequence LKFVEQNE (residues 169-176) and homologous sequences were found in proteins from Escherichia coli, Epstein-Barr virus, etc.
FRP
and its autoantibody may provide some clues to elucidate the process of disease development and a new approach to the design of therapeutics in RA.
...
PMID:Potential preventive effects of follistatin-related protein/TSC-36 on joint destruction and antagonistic modulation of its autoantibodies in rheumatoid arthritis. 1250 27
