miR-338-3p blocks TGF8-induced myofibroblast differentiation through the induction of PTEN

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease. The pathogenesis of IPF is not completely understood. However, numerous genes are associated with the development and progression of pulmonary fibrosis, indicating there is a significant genetic component to the pathogenesis of IPF. Epigenetic influences on the development of human disease, including pulmonary fibrosis, remain to be fully elucidated. In this paper, we identify miR-338-3p as a microRNA severely downregulated in the lungs of patients with pulmonary fibrosis and in experimental models of pulmonary fibrosis. Treatment of primary human lung fibroblasts with miR-338-3p inhibits myofibroblast differentiation and matrix protein production. Published and proposed targets of miR-338-3p such as TGF8 receptor 1, MEK/ERK 1/2, Cdk4, and Cyclin D are also not responsible for the regulation of pulmonary fibroblast behavior by miR-338-3p. miR-338-3p inhibits myofibroblast differentiation by preventing TGF8-mediated downregulation of phosphatase and tensin homolog (PTEN), a known antifibrotic mediator.

Automated summary

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a significant genetic component. miR-338-3p, severely downregulated in patients with pulmonary fibrosis, inhibits myofibroblast differentiation and plays a key role in regulating the behavior of fibroblasts.