Possible involvement of peptidylprolyl isomerase Pin1 in rheumatoid arthritis.
The peptidylprolyl isomerase Pin1 is over-expressed in some human diseases including malignancies and chronic inflammatory diseases, this suggests that it contributes to the constitutive activation of certain intracellular signaling pathways that promote cell proliferation and cell invasion. Here, we investigate the possible role of Pin1 in rheumatoid arthritis (RA). Pin1 expression was immunohistochemically analyzed in synovial tissue (ST) obtained from patients with RA and osteoarthritis (OA). To investigate the correlation between Pin1 and motility and proliferation of synovial cells, Pin1 localization was immunohistochemically compared with matrix metalloproteinase (MMP)-1, MMP-3, and proliferating cell nuclear antigen (PCNA). Double immunofluorescent staining for Pin1 and p65 was performed to determine whether Pin1 is involved in nuclear factor κB (NF-κB) activation in RA-ST. Results showed Pin1 expression was significantly higher in RA-ST than in OA-ST. The expression of MMP-1, MMP-3, and PCNA was also significantly elevated in RA-ST. Double immunofluorescent staining revealed colocalization of Pin1 and p65 in the nuclei of RA-ST. These results suggest that Pin1 may be involved in the pathogenesis of RA binding with p65 to activate the proteins MMP-1, MMP-3, and PCNA. Therefore, Pin1 may play a pivotal role in the pathogenesis of RA.
Department of Orthopaedic Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Akiko
A
Nagaoka
Naohiro
N
Takizawa
Ryohei
R
Takeuchi
Yutaka
Y
Inaba
Izumi
I
Saito
Yoji
Y
Nagashima
Tomoyuki
T
Saito
Ichiro
I
Aoki
D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008875:Middle Aged; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013582:Synovial Fluid / Q000166:cytology / Q000201:enzymology*
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D018809:Proliferating Cell Nuclear Antigen; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase