Protein/mRNA expression of cjun, junB, junD, and cfos, levels of the mRNA-destabilizing proteins AUF-1 and tristetraprolin (TTP), and levels of the mRNA-stabilizing protein HuR were assessed in synovial membranes (SM) from patients with rheumatoid arthritis (RA), osteoarthritis (OA), joint trauma (JT), or postmortem normal controls (NC) using ELISA/western blotting and real-time RT-PCR.
Protein expression for Jun/Fos proto-oncogenes was significantly increased (JunB and JunD) or numerically increased (cJun and cFos) in RA SM compared with OA, JT, and NC. In contrast, jun/fos mRNA expression was significantly decreased (cjun and junB) or numerically decreased (junD and cfos) in RA and OA compared with JT or NC.
Protein expression levels of AUF-1 were comparable among the different groups. For TTP and HuR, interestingly, significantly increased protein expression was observed in RA and OA SM compared with either JT or NC.
Discrepancies between the mRNA and protein expression for several jun/fos genes suggest broad alterations of post-transcriptional processes in the RA SM. Whereas increased levels of mRNA-destabilizing TTP may contribute to the low levels of jun/fos mRNA, abundant mRNA-stabilizing HuR may augment translation of the remaining mRNA into protein. As a consequence, both increased expression of AP-1-dependent target genes by the activating transcription factors cJun/cFos and modified binding activity of the resulting AP-1 complexes via the action of deactivating JunB and JunD may contribute to the pathogenesis of RA.
This work was supported by grants from the Interdisciplinary Center of Clinical Research Jena (including a grant for junior researchers to RH; FKZ 01ZZ9602/FKZ 01ZZ0105) and the Jena Centre for Bioinformatics (FKZ 0312704B). RH was also supported by a grant of the German National Academic Foundation.