Fibrosis- and Transforming Growth Factor-beta (TGF-beta) signaling pathway-related genes regulated by exosomal microRNAs (miRNAs)

The term "Fibrosis- and Transforming Growth Factor-beta (TGF-beta) signaling pathway-related genes regulated by exosomal microRNAs (miRNAs)" refers to a complex regulatory network central to the pathogenesis of various fibrotic disorders. The TGF-beta pathway is the master regulator of myofibroblast activation and extracellular matrix (ECM) production, primarily signaling through SMAD proteins (SMAD2/3/4) to induce genes like Collagen Type I Alpha 1 Chain (COL1A1) and Actin Alpha 2 (ACTA2) (Meng et al., 2016, Nature Reviews Nephrology). Exosomes, a type of extracellular vesicle, facilitate the horizontal transfer of miRNAs between cells, which can post-transcriptionally regulate the expression of these TGF-beta pathway components (Jiang et al., 2020, Molecular Therapy). For instance, exosomal miR-21 often amplifies TGF-beta signaling by inhibiting negative regulators like SMAD7, whereas the miR-29 family typically functions as an anti-fibrotic brake (Thum et al., 2008, Nature). Therapeutic strategies targeting this network include small molecule inhibitors of TGF-beta receptors (e.g., Galunisertib) and neutralizing antibodies (e.g., Fresolimumab). However, the pleiotropic nature of TGF-beta signaling presents significant challenges, as systemic inhibition can lead to adverse effects on immune function and tissue repair (Giannelli et al., 2014, Cancer Treatment Reviews).

Other names

TGF-beta signaling pathwayExosomal miRNA-regulated fibrotic genesTGF-beta/SMAD pathwaymiRNA-TGF-beta-fibrosis axis

Inhibition of TGF-beta receptor kinase activity, neutralization of TGF-beta ligands, or modulation of downstream SMAD signaling and miRNA-mediated gene silencing.