miR-338-3p blocks TGFβ-induced myofibroblast differentiation through the induction of PTEN.
Ashley R RackowJennifer L JudgeCollynn F WoellerPatricia J SimeRobert M KottmannPublished in: American journal of physiology. Lung cellular and molecular physiology (2022)
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 TGFβ 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 TGFβ-mediated downregulation of phosphatase and tensin homolog (PTEN), a known antifibrotic mediator.
Keyphrases
- pulmonary fibrosis
- idiopathic pulmonary fibrosis
- interstitial lung disease
- pi k akt
- cell proliferation
- transforming growth factor
- signaling pathway
- cell cycle
- endothelial cells
- genome wide
- cell cycle arrest
- dna methylation
- gene expression
- systemic sclerosis
- epithelial mesenchymal transition
- drug induced
- high glucose
- randomized controlled trial
- oxidative stress
- binding protein
- rheumatoid arthritis
- diabetic rats
- extracellular matrix
- small molecule
- protein protein
- amino acid
- genome wide identification