Mechanical Stretch Up-regulates MicroRNA-26a and Induces Human Airway Smooth Muscle Hypertrophy by Suppressing Glycogen Synthase Kinase-3β

摘要: Airway smooth muscle hypertrophy is one of the hallmarks airway remodeling in severe asthma. Several human diseases have been now associated with dysregulated microRNA (miRNA) expression. miRNAs are a class small non-coding RNAs, which negatively regulate gene expression at post-transcriptional level. Here, we identify miR-26a as hypertrophic miRNA cells (HASMCs). We show that stretch selectively induces transcription located locus 3p21.3 chromosome 3. The factor CCAAT enhancer-binding protein α (C/EBPα) directly activates through transcriptional machinery upon stretch. Furthermore, or enforced HASMC hypertrophy, and miR-26 knockdown reverses this effect, suggesting gene. glycogen synthase kinase-3β (GSK-3β), an anti-hypertrophic protein, target miR-26a. Luciferase reporter assays demonstrate interact 3′-untranslated repeat GSK-3β mRNA. Stretch attenuates endogenous levels followed by induction hypertrophy. miR-26a-induced occurs via its GSK-3β. Overall, first time, our study unveils mechanosensitive gene, it plays important role regulation