The Role of C/EBP-Homologous Protein in Idiopathic Inflammatory Myopathies.
Monica Sciacco, Patrizia Ciscato, Letizia Bertolasi, Maria Guttuso, Stefania Corti, Deborah Mattinzoli, Masami Ikeata, Giuseppe Castellano, Giacomo Pietro Comi, Simona Zanotti
Abstract
Open AccessThe Idiopathic Inflammatory Myopathies (IIMs) are a group of autoimmune disorders characterised by persistent muscle inflammation and diverse clinical manifestations. Common symptoms include muscle weakness, myalgia, and elevated serum creatine kinase levels. Recent findings highlight the relevance of muscle fibre necrosis in IIMs. We therefore grouped our IIM patients according to the percentage of necrotic fibres in muscle biopsy. Our clustered patients were analysed for the inflammatory milieu, the capillary network, and the endoplasmic reticulum stress. In patients with a higher percentage of necrotic fibres we detected a more marked presence of CD206 positive cells, an activation of the endothelial-mesenchymal transition process, an altered capillary network, more marked ER stress and connective tissue deposition. Furthermore, our study revealed a key role of C/EBP-homologous protein (CHOP), a multifunctional transcription factor that contributes to cellular functions including apoptosis, autophagy, inflammation, mediation of ER stress and induction of fibrosis. Our study suggests that CD206 positive cells and CHOP have an important role in pathogenetic mechanisms and could therefore be considered possible therapeutic targets to modulate the inflammatory response of these patients, namely to contain or slow down the progression of fibrosis.