Long noncoding RNA LINC-PINT retards the abnormal growth of airway smooth muscle cells via regulating the microRNA-26a-5p/PTEN axis in asthma

• Published in: International immunopharmacology 2021-10, Vol.99, p.107997-107997, Article 107997
• Main Authors: Gao, Pei, Ding, Ying, Yin, Bingru, Gu, Haoxiang
• Format: Article
• Language: English
• Subjects: Airway Remodeling; Airway smooth muscle cells; Animals; Assaying; Asthma; Asthma - genetics; Asthma - metabolism; Asthma - pathology; Becaplermin - pharmacology; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Cytokines - metabolism; Gelatinase B; Growth factors; Immunoglobulin E; Inflammation; Interstitial collagenase; long noncoding RNA LINC-PINT; Lung - pathology; Lungs; Matrix metalloproteinase; Matrix Metalloproteinases - metabolism; microRNA-26a-5p; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Models, Animal; Molecular modelling; Muscles; Myocytes, Smooth Muscle - metabolism; Ovalbumin; Platelet-derived growth factor; Platelet-derived growth factor BB; Protein expression; Proteins; PTEN; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; PTEN protein; Rats; Respiratory diseases; Respiratory System - metabolism; Respiratory System - pathology; Respiratory tract; Respiratory tract diseases; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Smooth muscle
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2021.107997

•LINC-PINT was down-regulated in asthmatic rats.•LINC-PINT constrained the PDGF-BB-stimulated abnormal growth of ASMCs.•LINC-PINT attenuated the AHR, airway inflammation, and lung pathological changes in asthmatic rats.•LINC-PINT inhibited the abnormal growth of ASMCs via regulating the miR-26a-5p/PTEN axis in asthma. Asthma is a chronic respiratory disease worldwide. This study aimed to explore the functions of the long noncoding RNA LINC-PINT (LINC-PINT) in asthma and to determine its underlying molecular mechanisms. Rat asthma model was established with ovalbumin sensitization and challenge. The serum level of IgE, airway hyperresponsiveness (AHR), airway inflammation, and pathological changes of lung were evaluated. Airway smooth muscle cells (ASMCs) were stimulated with platelet-derived growth factor-BB (PDGF-BB) to mimic the asthma-like condition at cellular level. QRT-PCR was performed to detect the expression of LINC-PINT, microRNA-26a-5p (miR-26a-5p), and PTEN. MTT and transwell assays were performed to measure the viability and migration of ASMCs. The protein expression of airway remodelling marker MMP-1 and MMP-9 was measured by western blot. The interactions among LINC-PINT, miR-26a-5p, and PTEN were determined by dual-luciferase reporter assay. The expression of LINC-PINT and PTEN was decreased, while miR-26a-5p expression was increased in PDGF-BB-stimulated ASMCs. In vivo, overexpression of LINC-PINT decreased the serum level of IgE, AHR, airway inflammation, and pathological changes of lung in asthma rat model. In vitro, up-regulation of LINC-PINT decreased the viability, migration, and MMP-1 and MMP-9 protein expression in PDGF-BB-stimulated ASMCs. Dual-luciferase reporter assay determined that LINC-PINT targeted miR-26a-5p, and miR-26a-5p targeted PTEN in ASMCs. Feedback approaches confirmed that miR-26a-5p up-regulation or PTEN down-regulation reversed the suppressive effect of LINC-PINT overexpression on the abnormal growth of ASMCs. LINC-PINT overexpression retarded the abnormal growth of ASMCs by regulating the miR-26a-5p/PTEN axis, offering a potential therapeutic target for asthma.