Abstract
Chronic obstructive pulmonary disease (COPD) is a complex disease with multiple etiologies, while smoking is the most established one. The present study investigated the modulation of T-helper 17 (Th17) cell differentiation by the miR-21/Smad7/TGF-β pathway, and their roles in COPD. Lung tissues were obtained from lung cancer patients with or without COPD who underwent lobotomy and the levels of miR-21, TGF-β/Smad signaling molecules, RORγT, and other Th17-related cytokines were detected. Mouse COPD models were built by exposing both wild-type (WT) and miR-21−/− mice to cigarette smoke (CS) and cigarette smoke extract (CSE) intraperitoneal injection. Isolated primary CD4+ T cells were treated with either CS extract, miR-21 mimics or inhibitors, followed by measuring Th17 cells markers and the expression of TGF-β/Smad signaling molecules and RORγT. Increased levels of miR-21, Smad7, phosphorylated (p)-Smad2, p-Smad3, TGF-β, and Th17-related cytokines was detected in the lungs of COPD patients. Lung function in modeled WT mice, but not miR-21−/− ones, deteriorated and the number of inflammatory cells in the lung tissues increased compared to the control WT-mice. Moreover, primary CD4+ lymphocytes tend to differentiate into Th17 cells after the treatment with CSE or miR-21 mimics, and the expression of RORγT and the TGF-β/Smad signaling were all increased, however miR-21 inhibitors worked reversely. Our findings demonstrated that Th17 cells increased under COPD pathogenesis and was partially modulated by the miR-21/Smad7/TGF-β pathway.
Highlights
Chronic obstructive pulmonary disease (COPD) is one of the most common causes of morbidity and mortality worldwide[1]
We found that the relative miR-21 levels in the lung tissues of the COPD patients were significantly increased compared to the levels in the non-smokers by using RT-qPCR (Fig. 1A).The levels of T-helper 17 (Th17)-related cytokines were quantified in the lung tissue homogenates of COPD patients and non-smokers using Enzyme‐linked immunosorbent assay (ELISA)
ROR-γT is Th17 related key transcription factor, Compared with non-smokers, the COPD patients had higher expression of ROR-γT in their lung tissues, which we confirmed using both RT-qPCR (Fig. 1H) and western blot analyses (Fig. 1I). These results suggest that there had high expression of both miR-21 and activation of Th17 cells in COPD patients
Summary
Chronic obstructive pulmonary disease (COPD) is one of the most common causes of morbidity and mortality worldwide[1]. Numerous studies have shown that cigarette smoking can induce infiltration of inflammatory cells into the lung[3].We found a massive infiltration of inflammatory cells in the lungs of COPD mice[4]. Th17 cells could further give rise to the persistent inflammation in lungs of COPD patients[5], resulting in uncontrollable airway and alveolar inflammation, damaging the lung tissue structures, and eventually leading to e mphysema[3,6]. Our group previously found that miR-21 expression was notably increased in the COPD rats, and we reconfirmed this result in the peripheral serum, mononuclear cells and circulation exosomes of COPD patients[8,9]. We hypothesized that miR-21 affects Th17 cell function in COPD patients. We proved the hypothesis that miR-21 plays a role in the pathogenesis of COPD by affecting Th17 cells functions through modulating the Smad7/TGF-β pathway
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
