Cross-Talk between Mitochondrial Dysfunction-Provoked Oxidative Stress and Aberrant Noncoding RNA Expression in the Pathogenesis and Pathophysiology of SLE

Abstract

Systemic lupus erythematosus (SLE) is a prototype of systemic autoimmune disease involving almost every organ. Polygenic predisposition and complicated epigenetic regulations are the upstream factors to elicit its development. Mitochondrial dysfunction-provoked oxidative stress may also play a crucial role in it. Classical epigenetic regulations of gene expression may include DNA methylation/acetylation and histone modification. Recent investigations have revealed that intracellular and extracellular (exosomal) noncoding RNAs (ncRNAs), including microRNAs (miRs), and long noncoding RNAs (lncRNAs), are the key molecules for post-transcriptional regulation of messenger (m)RNA expression. Oxidative and nitrosative stresses originating from mitochondrial dysfunctions could become the pathological biosignatures for increased cell apoptosis/necrosis, nonhyperglycemic metabolic syndrome, multiple neoantigen formation, and immune dysregulation in patients with SLE. Recently, many authors noted that the cross-talk between oxidative stress and ncRNAs can trigger and perpetuate autoimmune reactions in patients with SLE. Intracellular interactions between miR and lncRNAs as well as extracellular exosomal ncRNA communication to and fro between remote cells/tissues via plasma or other body fluids also occur in the body. The urinary exosomal ncRNAs can now represent biosignatures for lupus nephritis. Herein, we’ll briefly review and discuss the cross-talk between excessive oxidative/nitrosative stress induced by mitochondrial dysfunction in tissues/cells and ncRNAs, as well as the prospect of antioxidant therapy in patients with SLE.

Regulating the Polarization of Macrophages: A Promising Approach to Vascular Dermatosis

“…ROS and NO, the crucial mediators of vascular inflammation, are mostly derived from macrophages and potently involved in various vascular inflammatory diseases such as BD, SLE, atherosclerosis, and cancer [ 60 – 63 ]. During the early period of vascular inflammation, ROS and NO from macrophages benefit to eliminate the foreign pathogens [ 64 – 66 ].…”

“…In addition, ROS-induced OS damage is considered as another player in the pathogenesis of SLE and antioxidants targeting OS seem to be effective in SLE [ 128 ]. OS not only damages biomolecules to produce various autoantibodies in SLE [ 129 , 130 ] but also contributes to vascular endothelial cell injury and triggers lupus vasculitis [ 63 ]. Anyhow, M1 overactivation with M2 absence would aggravate the imbalance between Th1/Th17 and Th2/Treg cells, and accelerate OS damage to cells/tissues, further accelerating the progression of SLE.…”

Aberrant Non-Coding RNA Expression in Patients with Systemic Lupus Erythematosus: Consequences for Immune Dysfunctions and Tissue Damage

“…Epigenetics is the study of heritable changes in gene functions that occur without a change in genetic codes. The basis of epigenetic regulation of gene expression includes DNA methylation/acetylation, pre-transcriptional gene expression with chromatin remodeling by histone modifications, gene transcription by post-translational non-histone protein modifications, and intracellular and cell-free ncRNAs for post-transcriptional interference for mRNA expression [62]. The ncRNAs are arbitrarily divided into microRNAs (miR with 20-24 nucleotides) and long non-coding RNAs (lncRNAs with >300 nucleotides).…”

Lupus Eritematosus Sistemik pada Pria

“…1 Faktor genetik dan lingkungan diketahui berperan dalam patogenesis penyakit ini. 2 LES ditandai dengan pembentukan autoantibodi patogenik terhadap asam nukleat dan protein pengikatnya yang disebabkan oleh intoleransi terhadap komponen tubuh sendiri (selfintolerance). Lupus eritematosus sistemik memiliki manifestasi klinis, kelainan imunologi dan laboratorium, perjalanan penyakit, serta akibat penyakit yang beragam.…”