Journal
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
Volume 51, Issue 4, Pages -Publisher
WILEY
DOI: 10.1111/eci.13425
Keywords
airway remodelling; cigarette smoke; COPD; IL-6; let-7
Funding
- Natural Science Foundation of Wuxi [JZYX01]
- project of Jiangsu Commission of Health [BJ17009]
Ask authors/readers for more resources
This study observed decreased let-7 expression but increased IL-6 levels in COPD patients, CS-exposed mice, and CSE-treated human bronchial epithelial cells. Let-7 was shown to regulate myofibroblast differentiation and ECM deposition by targeting and silencing IL-6 through binding to its 3' UTR.
Background Myofibroblast differentiation and extracellular matrix (ECM) deposition are observed in chronic obstructive pulmonary disease (COPD). However, the mechanisms of regulation of myofibroblast differentiation remain unclear. Materials and methods We detected let-7 levels in peripheral lung tissues, serum and primary bronchial epithelial cells of COPD patients and cigarette smoke (CS)-exposed mice. IL-6 mRNA was explored in lung tissues of COPD patients and CS-exposed mice. IL-6 protein was detected in cell supernatant from primary epithelial cells by ELISA. We confirmed the regulatory effect of let-7 on IL-6 by luciferase reporter assay. Western blotting assay was used to determine the expression of alpha-SMA, E-cadherin and collagen I. In vitro, cell study was performed to demonstrate the role of let-7 in myofibroblast differentiation and ECM deposition. Results Low expression of let-7 was observed in COPD patients, CS-exposed mice and CS extract (CSE)-treated human bronchial epithelial (HBE) cells. Increased IL-6 was found in COPD patients, CS-exposed mice and CSE-treated HBE cells. Let-7 targets and silences IL-6 protein coding genes through binding to 3' untranslated region (UTR) of IL-6. Normal or CSE-treated HBE cells were co-cultured with human embryonic lung fibroblasts (MRC-5 cells). Reduction of let-7 in HBE cells caused myofibroblast differentiation and ECM deposition, while increase of let-7 mimics decreased myofibroblast differentiation phenotype and ECM deposition. Conclusion We demonstrate that CS reduced let-7 expression in COPD and, further, identify let-7 as a regulator of myofibroblast differentiation through the regulation of IL-6, which has potential value for diagnosis and treatment of COPD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available