Redox distress in organ fibrosis: The role of noncoding RNAs

Abstract Fibrosis is the formation of nonfunctional scar tissue in response to a nonresolving inflammation after a sustained injury. It is a consequence of the excessive accumulation of extracellular matrix proteins, whose synthesis is attributed to activated myofibroblasts. MicroRNAs (miRNAs) are short, 19–25 nucleotides (nt), noncoding RNAs involved in the posttranscriptional regulation of gene expression. They are now recognized as relevant players in the progression and establishment of organ fibrosis, through the modulation of processes such as TGF-β1 signaling, metabolic homeostasis, and chronic inflammation. The unbalance between reactive oxygen species (ROS) generation and antioxidant defense (redox distress) is an important contributor to fibrosis development in multiple organs. MiRNAs regulate the expression of genes involved in redox responses, and reciprocally, they are affected by the nucleophillic cellular tone. The identification of the subset of miRNAs regulating fibrogenesis through redox-based mechanisms and the comprehension of these mechanisms may prove useful for the diagnosis, prognosis, and treatment of organ fibrosis.