Roles of Exosome-Derived Noncoding RNA in Fibrosis

Fibrosis is a chronic, progressive disease characterized by the excessive accumulation of extracellular matrix (ECM) in tissues and organs during damage-repair responses. This pathological process can involve almost any tissue or organ and may eventually lead to organ failure, posing a major threat to human health. ECM production is closely related to intercellular communication. As one of the biologically active substances participating in intercellular communication, exosomes have attracted increasing attention in recent years. In particular, noncoding RNAs (ncRNAs) enriched in exosomes regulate gene expression at multiple levels and influence the fibrosis process. Common ncRNAs include miRNA, long ncRNAs, circRNA, and tRNA, which can be selectively loaded into exosomes by various cells to modulate receptor cell functions. In fibrosis-related diseases, the primary sources of exosome-derived ncRNAs (Exo-ncRNAs) include mesenchymal stem cells, macrophages, epithelial cells, and fibroblasts. These Exo-ncRNAs regulate macrophage polarization, epithelial-mesenchymal transition, and fibroblast-myofibroblast transdifferentiation within the microenvironment. In this review, we summarize the regulatory roles and molecular mechanisms of these ncRNAs in the fibrosis process, and discuss Exo-ncRNAs with potential therapeutic effects. Understanding Exo-ncRNAs from different cell sources may provide new research directions for pathological intervention and the treatment of multiorgan fibrosis.