Other fibrosis-related mRNAs regulated by miR-29

The miR-29 family, comprising miR-29a, miR-29b, and miR-29c, is a critical regulator of the fibrotic response across various tissues (PMID: 18066068). These microRNAs act as "master regulators" of the extracellular matrix (ECM) by targeting a wide array of mRNAs encoding structural proteins, such as various types of collagen (e.g., Collagen type I alpha 1 chain, Collagen type III alpha 1 chain), elastin (ELN), and fibrillin (FBN1), as well as enzymes involved in ECM cross-linking like lysyl oxidase (LOX) (PMID: 20810911). In fibrotic diseases, miR-29 expression is typically downregulated, leading to the pathological overproduction of these ECM components (PMID: 20523150). Therapeutic strategies often involve the use of miR-29 mimics, such as Remlarsen (MRG-201), to restore miR-29 levels and suppress the expression of these pro-fibrotic mRNAs (PMID: 30670910). While promising, targeting a broad set of mRNAs presents challenges regarding specificity and potential off-target effects in non-fibrotic tissues (PMID: 25100223). This collective group of targets represents a multi-nodal therapeutic approach to treating complex fibrotic disorders.

Other names

miR-29 target genesPro-fibrotic mRNAs regulated by miR-29miR-29-regulated extracellular matrix genesCollagen type I alpha 1 chain (COL1A1)Collagen type III alpha 1 chain (COL3A1)Elastin (ELN)Fibrillin 1 (FBN1)Lysyl oxidase (LOX)Integrin beta 1 (ITGB1)Matrix metallopeptidase 2 (MMP2)

Agonism of the miR-29 pathway via synthetic mimics leads to the sequence-specific degradation or translational inhibition of target mRNAs, resulting in decreased synthesis of extracellular matrix proteins and attenuation of fibrosis.