MicroRNA-29 regulated profibrotic messenger RNAs (miR-29 target mRNAs)

Profibrotic mRNAs with miR-29 response elements represent a network of messenger RNAs that encode structural components of the extracellular matrix (ECM) and are post-transcriptionally regulated by the microRNA-29 (miR-29) family. This group includes transcripts for various collagens (e.g., COL1A1, COL1A2, COL3A1), elastin (ELN), and fibrillin (FBN1), which contain conserved miR-29 binding sites in their 3' untranslated regions (Maurer et al., 2010, 'MicroRNA-29, a key regulator of collagen expression in systemic sclerosis'). In healthy tissues, miR-29 maintains ECM homeostasis by suppressing the translation of these mRNAs; however, in fibrotic diseases, miR-29 levels are typically downregulated, leading to the pathological overproduction of ECM proteins (He et al., 2013, 'The miR-29 family: a central regulator of fibrosis'). Therapeutic intervention involves the use of miR-29 mimics, such as Remlarsen (MRG-201), which bind to these response elements to restore inhibitory control and reduce fibrosis (Gallant-Behm et al., 2019, 'Remlarsen (MRG-201), a Mimic of microRNA-29, Reduces Skin Fibrosis'). This target class is unique because it allows for the simultaneous modulation of multiple genes within a single pathogenic pathway, potentially offering greater efficacy than single-protein inhibitors. Clinical development has primarily focused on cutaneous fibrosis, idiopathic pulmonary fibrosis, and cardiac remodeling (Montgomery et al., 2014, 'Therapeutic inhibition of miR-29 promotes systemic fibrosis').

Other names

miR-29 targetsmiR-29 regulated gene networkExtracellular matrix mRNAs with miR-29 binding sitesProfibrotic gene network regulated by miR-29

MicroRNA mimicry leading to sequence-specific binding to 3' UTRs and subsequent mRNA degradation or translational repression of profibrotic genes.