Increase in Transglutaminase 2 in Idiopathic Inflammatory Myopathies

Abstract

Idiopathic inflammatory myopathies (IMs), including dermatomyositis (DM), polymyositis (PM), and sporadic inclusion body myositis (s-IBM), are characterized by inflammatory cell infiltration in muscle tissue and muscle fiber destruction, which leads to muscle weakness. Although the cause of IMs is unclear, an autoimmune pathogenesis may be involved in initiating the muscle inflammation. Recently, we have found an aberrant expression of transglutaminase 2 (TGase 2) in s-IBM, which is closely associated with insoluble inclusion body formation. TGase 2 is a cross-linking enzyme that generates a conformational change of molecules via a covalent isopeptide bond. The increase in the level of TGase 2 expression and the inappropriate presentation of substrates/cross-linked aggregates to the immune system may contribute to the autoimmune aspects of IMs. We investigated whether or not an increase in TGase 2 expression is a common factor in muscle inflammation. Duchenne muscular dystrophy (DMD) and normal tissues were employed as controls. Using immunocytochemistry and quantitative RT-PCR, the level of TGase 2 expression was found to be specifically increased in PM and DM, but not in DMD and normal controls. Therefore, the targeting of TGase inhibition in IMs will be a challenging therapeutic approach that should be investigated in the near future.