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Clinicopathological correlations of podoplanin (gp38) expression in rheumatoid synovium and its potential contribution to fibroblast platelet crosstalk
9 p.-4 fig.-2 tab.Introduction: Synovial fibroblasts (SF) undergo phenotypic changes in rheumatoid arthritis (RA) that contribute to
inflammatory joint destruction. This study was undertaken to evaluate the clinical and functional significance of ectopic podoplanin (gp38) expression by RA SF.
Methods: Expression of gp38 and its CLEC2 receptor was analyzed by immunohistochemistry in synovial arthroscopic
biopsies from RA patients and normal and osteoarthritic controls. Correlation between gp38 expression and RA
clinicopathological variables was analyzed. In patients rebiopsied after anti-TNF-a therapy, changes in gp38 expression were
determined. Platelet-SF coculture and gp38 silencing in SF were used to analyze the functional contribution of gp38 to SF
migratory and invasive properties, and to SF platelet crosstalk.
Results: gp38 was abundantly but variably expressed in RA, and it was undetectable in normal synovial tissues. Among
clinicopathologigal RA variables, significantly increased gp38 expression was only found in patients with lymphoid
neogenesis (LN), and RF or ACPA autoantibodies. Cultured synovial but not dermal fibroblasts showed strong constitutive
gp38 expression that was further induced by TNF-a. In RA patients, anti-TNF-a therapy significantly reduced synovial gp38
expression. In RA synovium, CLEC2 receptor expression was only observed in platelets. gp38 silencing in cultured SF did not
modify their migratory and invasive properties but reduced the expression of IL-6 and IL-8 genes induced by SF-platelet
interaction.
Conclusions: In RA, synovial expression of gp38 is strongly associated to LN and it is reduced after anti-TNF-a therapy.
Interaction between gp38 and CLEC2 platelet receptor is feasible in RA synovium in vivo and can specifically contribute ton gene expression by SF.This study was supported by Instituto de Salud Carlos III (FIS 12/439, RETICS RD12/0009 RIER, and RÃo Hortega program to R. F.), and Comunidad de Madrid (S2010/BMD2350, RAPHYME).Peer reviewe