The Role of MiR-29 in the Mechanism of Fibrosis

Abstract

Fibrosis is a pathological process characterized by tissue scarring that can occur in various human body organs. The fibrosis of the organ is manifested as an increase in fibrous connective tissue and a decrease in parenchymal cells in the organ tissue, leading to structural damage and functional decline of the organ. At present, the incidence and medical burden of fibrosis are increasing worldwide, which has presented severe negative impacts on human health. Although many of the cellular and molecular processes for underlying fibrosis have been discerned, there are still gaps for effective therapies and target fibrogenesis specifically. Recent studies have shown that the microRNA- 29 family (miR-29a, b, c) plays an essential role in the process of multiorgan fibrosis. It is a class of highly conserved single-stranded noncoding RNAs composed of 20-26 nucleotides. Through its 5' untranslated region (UTR) pairing with the 3'UTR of the target mRNA, the mRNA of the target gene is degraded to complete the physiological process of inhibiting the transcription and translation of the target gene. Here, we summarize the interaction of miR-29 with multiple cytokines, describe the mechanism by which miR-29 regulates major fibrotic pathways such as TGF- β1/Smad, PI3K/Akt/mTOR, DNA methylation, and found that miR-29 is closely linked to epithelial- mesenchymal transition (EMT). These findings point to a common or similar regulatory mechanism by miR-29 in fibrogenesis. Finally, we review the antifibrotic activity of miR-29 mimicked in current studies and highlight miR-29 as a promising therapeutic reagent or target for the treatment of pulmonary fibrosis. Besides, there is an urgent need to screen and identify small compounds to modulate miR-29 expression in vivo.

Keywords: TGF-β1; cytokine; fibrosis; miR-29; pathway; targeted therapy.