The Expression of Non-Coding RNAs and Their Target Molecules in Rheumatoid Arthritis: A Molecular Basis for Rheumatoid Pathogenesis and Its Potential Clinical Applications
Journal
International journal of molecular sciences
Journal Volume
22
Journal Issue
11
Pages
5689
Date Issued
2021-05-26
Author(s)
Tsai, Chang-Youh
Liu, Chih-Wei
Liao, Hsien-Tzung
Chen, Ming-Han
Abstract
Rheumatoid arthritis (RA) is a typical autoimmune-mediated rheumatic disease presenting as a chronic synovitis in the joint. The chronic synovial inflammation is characterized by hyper-vascularity and extravasation of various immune-related cells to form lymphoid aggregates where an intimate cross-talk among innate and adaptive immune cells takes place. These interactions facilitate production of abundant proinflammatory cytokines, chemokines and growth factors for the proliferation/maturation/differentiation of B lymphocytes to become plasma cells. Finally, the autoantibodies against denatured immunoglobulin G (rheumatoid factors), EB virus nuclear antigens (EBNAs) and citrullinated protein (ACPAs) are produced to trigger the development of RA. Furthermore, it is documented that gene mutations, abnormal epigenetic regulation of peptidylarginine deiminase genes 2 and 4 (PADI2 and PADI4), and thereby the induced autoantibodies against PAD2 and PAD4 are implicated in ACPA production in RA patients. The aberrant expressions of non-coding RNAs (ncRNAs) including microRNAs (miRs) and long non-coding RNAs (lncRNAs) in the immune system undoubtedly derange the mRNA expressions of cytokines/chemokines/growth factors. In the present review, we will discuss in detail the expression of these ncRNAs and their target molecules participating in developing RA, and the potential biomarkers for the disease, its diagnosis, cardiovascular complications and therapeutic response. Finally, we propose some prospective investigations for unraveling the conundrums of rheumatoid pathogenesis.
Subjects
RANK-RANKL-OPG signaling; Wnt/β-catenin pathway; anti-citrullinated protein antibody; bone-marrow-derived stem cell; fibroblast-like synoviocyte; non-coding RNA; peptidylarginine deiminase; rheumatoid arthritis
SDGs
Other Subjects
autoantibody; cyclic citrullinated peptide antibody; long untranslated RNA; microRNA; protein arginine deiminase type 2; protein arginine deiminase type 2 antibody; protein arginine deiminase type 4; protein arginine deiminase type 4 antibody; rheumatoid factor; unclassified drug; untranslated RNA; long untranslated RNA; PADI2 protein, human; PADI4 protein, human; antibody production; bone destruction; bone development; bone marrow mesenchymal stem cell; bone metabolism; cardiovascular disease; cell level; cell polarity; chronic inflammation; enzyme activity; exosome; fibroblast like synoviocyte; gene expression; human; immunopathogenesis; inflammation; interactions with RNA; macrophage; molecular interaction; nonhuman; protein expression; Review; rheumatic disease; rheumatoid arthritis; RNA blood level; synoviocyte; T lymphocyte subpopulation; biosynthesis; gene expression regulation; genetic epigenesis; genetics; metabolism; pathology; rheumatoid arthritis; Arthritis, Rheumatoid; Epigenesis, Genetic; Gene Expression Regulation, Enzymologic; Humans; Protein-Arginine Deiminase Type 2; Protein-Arginine Deiminase Type 4; RNA, Long Noncoding
Publisher
MDPI
Type
review