Immunohistological localization of Notch receptors and their ligands Delta and Jagged in synovial tissues of rheumatoid arthritis.
BACKGROUND
The interaction of Notch receptors with their transmembrane ligands Delta and Jagged plays an important role not only in the organization of a variety of tissues but also in several genetic disorders and cancer development. The functional involvement of the Notch signaling in rheumatoid arthritis (RA) has been reported previously, but the expression profile of Notch-related molecules, as well as their relation with clinicopathological parameters, remains unclear.


METHODS
In this study, we analyzed the immunohistochemical staining pattern of four Notch receptors (Notch1-4) and their ligands (Delta1 and Jagged1) in 14 synovial tissues obtained from 14 RA patients.


RESULTS
Notch2 and Notch4 were expressed in limited areas in a few samples or in small blood vessels, respectively. Notch1, Notch3, Delta1, and Jagged1 were overexpressed in the synovial lining and sublining cells on synovial hyperplastic lesions in all samples. Notch1 expression was also observed in T and B lymphocytes of lymphoid follicles independently. Notch1 and Notch3 expression overlapped with that of Jagged1, as determined by confocal microscopy. Activation of Notch1 signaling in the RA synovium was identified using a specific antibody to the cleaved form of Notch1. The expression of these molecules did not show any correlation with clinicopathological parameters.


CONCLUSIONS
Our results suggest that Notch signaling is activated in RA synovium but does not necessarily reflect the pathological condition of RA.
Yabe
Yoshihiro
Y
Department of Orthopaedic Surgery, Mitsubishi Nagasaki Hospital, 1-37 Koinoura, Nagasaki, 852-8588, Japan.
Matsumoto
Tomoko
T
Tsurumoto
Toshiyuki
T
Shindo
Hiroyuki
H
D000293:Adolescent; D000328:Adult; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism* / Q000473:pathology
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D020033:Protein Isoforms; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; C064045:delta protein