The role of micro RNA RNA ‐5196 in the pathogenesis of systemic sclerosis

摘要

Abstract Background Systemic sclerosis ( SS c) is a chronic autoimmune disease characterised by tissue fibrosis and immune abnormalities. Recent evidence suggests that activated circulating monocytes from patients with SS c play an important role in early stages of SS c pathogenesis due to enhanced expression of tissue inhibitor of metalloproteinases 1 ( TIMP ‐1), IL ‐8 and reactive oxygen species ( ROS ) induction. However, the exact factors that contribute to chronic inflammation and subsequently fibrosis progression are still unknown. Materials and methods The expression pattern of IL ‐8, TIMP ‐1, AP ‐1 transcription factor‐Fra2 and ROS induction in peripheral blood monocytes following DZN ep (histone methyltransferase inhibitor) and TLR 8 agonist stimulation was investigated. Exogenous micro RNA ‐5196, which is predicted to bind 3′ UTR of Fra2 gene, was delivered to reverse profibrotic phenotype in monocytes. Expression of circulating micro RNA ‐5196 was correlated with SS c parameters. Results DZN ep?+? TLR 8 agonist stimulation enhanced profibrotic TIMP ‐1, IL ‐8 and ROS generation in HC and SS c monocytes. As opposed by the decrease of mi RNA ‐5196 and antioxidant SOD 1 expression in SS c monocytes. Exogenous delivery of micro RNA ‐5196 reduced Fra2 and TIMP ‐1 expression suggesting that it may be used as a potential modulator of fibrogenesis in SS c. Circulating micro RNA ‐5196 was significantly increased in SS c and positively correlated with CRP level but not with Rodnan skin score or ESR . Conclusions These results suggest that micro RNA ‐5196 can be used as a potential biomarker characterising SS c. Overall, this study may open new possibilities for the development of micro RNA ‐5196‐based diagnostics and therapy in early phases of SS c.