MicroRNA-223 inhibits deposition of the extracellular matrix by airway smooth muscle cells through targeting IGF-1R in the PI3K/Akt pathway.
Year: 2018
Type: article
Abstract: Asthma is a wide-spread disease that significantly impacts health throughout the world. A key aspect of the pathology of the disease is the remodeling of the airways by airway smooth muscle cells (ASMCs). MicroRNAs play an important role in post-transcriptional gene regulation and are involved in numerous biological functions, including those linked to asthma. A large number of microRNAs have been identified and investigated in various cell types to assess their function. In the present study, the role and potential mechanisms of miR-223 in ASMCs were investigated. Overexpression of miR-223 was found to induce a phenotypic switch in ASMCs that led to decreased expression of proteins involved in the extracellular matrix, such as α-SMA (ACTA2), and type I and III collagens. Inhibition of miR-223 caused the opposite result. However, unlike mast cells, neither overexpression nor inhibition of miR-223 affected cell viability or apoptosis in ASMCs. To further understand the effects of miR-223 on ASMCs, we applied bioinformatics analysis using predictive software, in combination with western blotting, to reveal that insulin-like growth factor-1 receptor (IGF-1R) was the functional target of miR-223 that leads to the phenotypic switch of ASMCs. Suppression of luciferase activity in a reporter containing the 3'-untranslated region (3'-UTR) of IGF-1R confirmed that this region is the target for the miRNA. Finally, we showed that miR-223 suppressed IGF-1R expression and decreased downstream phosphorylation of Akt (AKT1) in ASMCs. In conclusion, our data demonstrate that miR-223 exerts an inhibitory effect on the fibrotic phenotypes of ASMCs via the PI3K/Akt signaling pathway and IGF-1R is the likely functional target of the microRNA.
Source: PubMed
Authors: Dongdong Liu, Jing Pan, Deyu Zhao, Feng Liu
Institutions: Nanjing Children's Hospital, Jiangsu Province Hospital
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3003544853