Research Paper Advance Articles

Exposure to ozone impacted Th1/Th2 imbalance of CD4+ T cells and apoptosis of ASMCs underlying asthmatic progression by activating lncRNA PVT1-miR-15a-5p/miR-29c-3p signaling

Yangyang Wei1, *, , Baofen Han1, *, , Wenjuan Dai1, , Shufang Guo1, , Caiping Zhang1, , Lixuan Zhao2, , Yan Gao2, , Yi Jiang1, , Xiaomei Kong1, ,

  • 1 Department of Respiratory and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan 030001, China
  • 2 Department of Medicine, Shanxi Medical University, Taiyuan 030001, China
* Equal contribution

Received: January 12, 2020       Accepted: September 13, 2020       Published: November 20, 2020      

https://doi.org/10.18632/aging.104124
How to Cite

Copyright: © 2020 Wei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

This investigation attempted to elucidate whether lncRNA PVT1-led miRNA axes participated in aggravating ozone-triggered asthma progression. One hundred and sixty-eight BALB/c mice were evenly divided into saline+air group, ovalbumin+air group, saline+ozone group and ovalbumin+ozone group. Correlations were evaluated between PVT1 expression and airway smooth muscle function/inflammatory cytokine release among the mice models. Furthermore, pcDNA3.1-PVT1 and si-PVT1 were, respectively, transfected into CD4+T cells and airway smooth muscle cells (ASMCs), and activities of the cells were observed. Ultimately, a cohort of asthma patients was recruited to estimate the diagnostic performance of PVT1. It was demonstrated that mice of ovalbumin+ozone group were associated with higher PVT1 expression, thicker trachea/airway smooth muscle and smaller ratio of Th1/Th2-like cytokines than mice of ovalbumin+air group and saline+ozone group (P<0.05). Moreover, pcDNA3.1-PVT1 significantly brought down Th1/Th2 ratio in CD4+ T cells by depressing miR-15a-5p expression and activating PI3K-Akt-mTOR signaling (P<0.05). The PVT1 also facilitated ASMC proliferation by sponging miR-29c-3p and motivating PI3K-Akt-mTOR signaling (P<0.05). Additionally, PVT1 seemed promising in diagnosis of asthma, with favorable sensitivity (i.e. 0.844) and specificity (i.e. 0.978). Conclusively, lncRNA PVT1-miR-15a-5p/miR-29c-3p-PI3K-Akt-mTOR axis was implicated in ozone-induced asthma development by promoting ASMC proliferation and Th1/Th2 imbalance.

Abbreviations

OVA: ovalbumin; ASMCs: airway smooth muscle cells; MCH: methacholine; AHR: airway hyper-responsiveness; HA: hyaluronan; HE: hemotoxylin-eosin; PI: propidium iodide; PVDF: polyvinylidene fluoride; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; HRP: horseradish peroxidase.