Nociceptive related microRNAs and their role in rheumatoid arthritis
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MINI REVIEW ARTICLE
Nociceptive related microRNAs and their role in rheumatoid arthritis S. Reyes‑Long1,3 · J. L. Cortes‑Altamirano1 · D. Clavijio‑Cornejo2 · M. Gutiérrez2 · C. Bertolazzi2 · C. Bandala1,3 · C. Pineda2 · A. Alfaro‑Rodríguez1 Received: 12 May 2020 / Accepted: 26 July 2020 © Springer Nature B.V. 2020
Abstract Rheumatoid Arthritis (RA) is an autoimmune disease with unknown etiology and a global incidence around 1%, a positive family history increases the risk of RA roughly three to five times. Pain is one of the first symptoms to appear in this disease. MicroRNAs (miRNAs) belong to the class of small non-coding RNAs; they regulate multiple cellular processes including embryonic development, cellular proliferation, differentiation and apoptosis among others. A great deal of evidence points to the employment of miRNAs as therapeutic targets and biomarkers for several pathologies. The main objective of this Review is to assess how miRNAs participate in the pathogenesis of RA. Two advanced searches were conducted in databases, one using “micro-RNA” and “rheumatoid arthritis” as key words, and another one with “micro-RNA”, “pain” and “nociception”. In this Review, we describe how six miRNAs: miR-16-5p, miR-23b-3b, miR-124-3p, miR-146a-5p, miR-155-5p and miR223-3p, involved in the modulation and transmission of the nociceptive input are unregulated in RA patients. Key molecular pathways involved in nociception, inflammation and autoimmune responses, are regulated by these miRNAs; the NF-κB, TNF-α, interleukins and TLR4. By means of gene repression, the miRNAs here described modulate the nociceptive process as well as the autoimmune response that characterize this disease. Keywords Rheumatoid arthritis · Pain · Micro-RNA · miRNA · Nociception
Introduction Rheumatoid arthritis (RA) is a systemic autoimmune disorder of unknown etiology in which genetics, epigenetics, and environmental aspects are considered as main risk factors that contribute to the development of this chronic disease. According to the World Health Organization, RA has a worldwide incidence, around 1%. An inflammatory process mainly located at joint and tendon levels, but with frequent extra-articular manifestations, at skin, lung, cardiovascular * A. Alfaro‑Rodríguez [email protected] 1
Department of Neurosciences, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Calzada México‑Xochimilco 289, Col. Arenal de Guadalupe, Del. Tlalpan, 14389 Mexico City, Mexico
2
Department of Musculoskeletal and Rheumatic Diseases, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico
3
Escuela Superior de Medicina, Instituto Politécnico Nacional, Salvador Díaz Mirón, Col. Casco de Santo Tomas, 11340 Mexico City, Mexico
system level characterize this disease, if untreated it may cause a considerable organ-tissue damage causing disability and reduction in patient’s quality of life and life expectancy [1]. The understanding of the pathophysiology and the underlying mechanisms that caus
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