De Bleecker, Jan

De Paepe, Boel

Ronnelid, Johan

Schmidt, Jens

English

Ghent University Academic Bibliography

AUTO16PS52-PARALLEL SESSION 52: THE AUTOIMMUNE ASPECTS OF PSORIASIS, MYOSITIS AND ATHEROSCLEROSISAbstract: 378OSMOREGULATORY PATHWAYS ARE ACTIVATED IN POLYMYOSITIS: INCREASED EXPRESSIONOF OSMOLYTE ACCUMULATORS IN MUSCLE FIBERS AND IMMUNE CELLSB. De Paepe1, J. Ronnelid2, S. Jens3, J. De Bleecker41Ghent University Hospital, Neuromuscular Reference Center, Ghent, Belgium 2Uppsala University, Clinical Immunology, Uppsala, Sweden 3Goettingen University, Neurology, Goettingen, Germany 4Ghent University, Neurology, Ghent, Belgium Background: Nuclear factor of activated T-cells 5 (NFAT5), the central regulator of cellular response to osmotic stress and inducer ofpro-inflammatory pathways, is involved in inflammatory muscle disease. Design: We studied the expression of molecular NFAT5targets involved in osmolyte accumulation, being aldose reductase (AR), taurine transporter (TauT) and sodium myo-inositol co-transporter (SMIT) in polymyositis (n=8) comparing with healthy muscle tissues (n=20) and using fluorescent immunolocalisation andwestern blotting. Results: In normal skeletal muscle, NFAT5 staining was present in myonuclei, and the sarcoplasm containedconstitutive levels of AR. TauT and SMIT staining was, on the other hand, absent from fibers in normal muscle. In polymyositis, AR wasincreased in the atrophic fibers, TauT showed patchy sarcoplasmic staining mostly in CD56+ regenerating muscle fibers, and SMITstaining was membranous (variable in intensity and often discontinuous). The vast majority of inflammatory cells were AR and TauTnegative, while many CD68+ and CD206+ type 2 macrophages and CD3+ T-cells were SMIT positive. Most CD68+ macrophagesinvading nonnecrotic muscle fibers were SMIT negative, while invading CD8+ cytotoxic T-cells were often SMIT positive. Quantitativewestern blotting could not detect TauT and SMIT in healthy muscle, but did detect the proteins in polymyositis samples. AR levels weresignificantly higher in polymyositis (0.83Â±0.06) than in control (0.52Â±0.10) and dermatomyositis (0.45Â±0.01) muscle samples.Conclusions: Osmolyte pathways are activated in polymyositis, indicating that osmoregulation may represent an importantpathologic mechanism.

Osmoregulatory pathways are activated in polymyositis: increased expression of osmolyte accumulators in muscle fibers and immune cells

https://biblio.ugent.be/publication/7183596/file/7183599

Osmoregulatory pathways are activated in polymyositis: increased expression of osmolyte accumulators in muscle fibers and immune cells

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Ghent University Academic Bibliography