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Discrepancy between Jun/Fos Proto-Oncogene mRNA and Protein Expression in the Rheumatoid Arthritis Synovial Membrane

1
Experimental Rheumatology Unit, Department of Orthopedics, Jena University Hospital, Waldkliniken Eisenberg GmbH, 07607 Eisenberg, Germany
2
Institute of Clinical Chemistry, Hannover Medical School, 30625 Hannover, Germany
3
Department of Rheumatology and Clinical Immunology, Charité University Hospital, Humboldt University Berlin, 10117 Berlin, Germany
*
Author to whom correspondence should be addressed.
J 2020, 3(2), 181-194; https://doi.org/10.3390/j3020015
Received: 13 March 2020 / Revised: 27 April 2020 / Accepted: 1 May 2020 / Published: 5 May 2020
Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease characterized by overexpression of pro-inflammatory/pro-destructive mediators, whose regulation has been the focus of our previous studies. Since the expression of these proteins commonly depends on AP-1, the expression of the AP-1-forming subunits cJun, JunB, JunD, and cFos was assessed in synovial membrane (SM) samples of RA, osteoarthritis (OA), joint trauma (JT), and normal controls (NC) using ELISA and qRT-PCR. With respect to an observed discrepancy between mRNA and protein levels, the expression of the mRNA stability-modifying factors AU-rich element RNA-binding protein (AUF)-1, tristetraprolin (TTP), and human antigen R (HuR) was measured. JunB and JunD protein expression was significantly higher in RA-SM compared to OA and/or NC. By contrast, jun/fos mRNA expression was significantly (cjun) or numerically decreased (junB, junD, cfos) in RA and OA compared to JT and/or NC. Remarkably, TTP and HuR were also affected by discrepancies between their mRNA and protein levels, since they were significantly decreased at the mRNA level in RA versus NC, but significantly or numerically increased at the protein level when compared to JT and NC. Discrepancies between the mRNA and protein expression for Jun/Fos and TTP/HuR suggest broad alterations of post-transcriptional processes in the RA-SM. In this context, increased levels of mRNA-destabilizing TTP may contribute to the low levels of jun/fos and ttp/hur mRNA, whereas abundant mRNA-stabilizing HuR may augment translation of the remaining mRNA into protein with potential consequences for the composition of the resulting AP-1 complexes and the expression of AP-1-dependent genes in RA. View Full-Text
Keywords: rheumatoid arthritis; Jun; Fos; mRNA expression; protein expression; discrepancy; mRNA stability; tristetraprolin; human antigen R rheumatoid arthritis; Jun; Fos; mRNA expression; protein expression; discrepancy; mRNA stability; tristetraprolin; human antigen R
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MDPI and ACS Style

Huber, R.; Stuhlmüller, B.; Kunisch, E.; Kinne, R.W. Discrepancy between Jun/Fos Proto-Oncogene mRNA and Protein Expression in the Rheumatoid Arthritis Synovial Membrane. J 2020, 3, 181-194. https://doi.org/10.3390/j3020015

AMA Style

Huber R, Stuhlmüller B, Kunisch E, Kinne RW. Discrepancy between Jun/Fos Proto-Oncogene mRNA and Protein Expression in the Rheumatoid Arthritis Synovial Membrane. J. 2020; 3(2):181-194. https://doi.org/10.3390/j3020015

Chicago/Turabian Style

Huber, René, Bruno Stuhlmüller, Elke Kunisch, and Raimund W. Kinne 2020. "Discrepancy between Jun/Fos Proto-Oncogene mRNA and Protein Expression in the Rheumatoid Arthritis Synovial Membrane" J 3, no. 2: 181-194. https://doi.org/10.3390/j3020015

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