LncRNA PVT1 exacerbates the inflammation and cell‐barrier injury during asthma by regulating miR‐149

Abstract

Background Asthma is a prevailing respiratory disease among children, characterized by allergic airway inflammation, airway remodeling, and airway hyperresponsiveness. Although it is well‐known that long non‐coding RNAs (lncRNAs) are linked to a variety of human diseases and well‐documented, very few studies explore its role in asthma. In this study, we investigate the effects of lncRNA PVT1 on the promotion of airway inflammation and its associated mechanisms. Methods and Materials Human small airway epithelial cells (HSAECs) with PVT1 overexpressed or knocked down were constructed, and platelet activating factor (PAF) was used to treat HSAECs to mimic the pathological process of asthma in vitro. The expressions of prostaglandin E2 (PGE2), interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α) were measured by enzyme‐linked immunosorbent assay (ELISA). The expressions of PKC, MyD88, and NF‐ĸB were measured by Western blot. Monolayer permeability of HSAECs was also compared within different groups. Luciferase reporter gene assay was employed to detect the targeting relationship between PVT1 and miR‐149. Results The knockdown of PVT1 attenuated the levels of inflammatory factors induced by PAF and destruction of cell‐barrier function. The overexpression of PVT1 facilitated the pathological development. Additionally, miR‐149 was identified as a target microRNA of PVT1, and the overexpression of miR‐149 could reverse the effects of PVT1 on PAF‐induced HSAECs. Conclusion These findings suggest that PVT1 may represent a novel potential target for treatment of asthma.

MicroRNA miR-146a-5p inhibits the inflammatory response and injury of airway epithelial cells via targeting TNF receptor-associated factor 6

“…Many studies have found that miRNA is crucial in cell differentiation, proliferation and apoptosis, and is related to many human diseases, such as cancer, chronic obstructive pulmonary disease, and interstitial lung disease, and asthma [ 26–31 ]. MiR-19a expression is dramatically raised in T lymphocytes infiltrated in the airway of asthma, and miR-19a can regulate PTEN, SOCS1 and A20 to cooperatively induce the production of Th2 cytokines [ 29 ]; miR-142-3p takes part in regulating the multiplication and differentiation of airway smooth muscle cells in asthma by inhibiting WNT signaling pathway [ 30 ]; miR-149 overexpression can inhibit inflammatory cytokines’ expressions in HSAECs induced by PAF, and alleviate the barrier damage of epithelial cells [ 31 ]. Here we reported that miR-146a-5p expression was declined in the blood samples of asthma individuals and PAF-stimulated HSAECs; miR-146a-5p overexpression can inhibit the secretion of inflammatory cytokines in HSAECs treated by PAF, alleviate the barrier damage of epithelial cells, and effectively inhibit the apoptosis.…”

Comprehensive Analysis of the Profiles of Differentially Expressed mRNAs, lncRNAs, and circRNAs in Phosgene-Induced Acute Lung Injury

“…For example, Fabp4 inhibitors suppress inflammation and oxidative stress in murine and cell models of acute lung injury [ 23 ], and suppression of Fabp4 protects against rhabdomyolysis-induced acute kidney injury [ 24 ]. In chronic obstructive pulmonary disease patients, the PVT1 expression positively correlated with the GOLD stage and levels of TNF- α , IL-6, IL-8, and IL-17 [ 25 ]; PVT1 exacerbates the inflammation and cell-barrier injury during asthma by regulating miR-149 [ 26 ]. These findings suggested that Fabp4 and PVT1 might play the role in the therapeutic potential of MSCs in phosgene-induced ALI, and we will research the potential role of them in the phosgene-induced ALI in the following research.…”

The lncRNA PVT1/miR-423-5p axis is positively correlated with the severity of bronchial asthma

“…25 PVT1 knockdown inhibited the levels of inflammatory factors in asthma. 11 Altogether, lncRNA PVT1 and lncRNA PVT1/miR-423-5p axis were associated with increased severity of BA while miR-423-5p was negatively correlated with BA severity.…”

“…9,10 Based on the existing study, lncRNA plasmacytoma variant translocation 1 (PVT1) might be important in asthma and lncRNA PVT1 exacerbates inflammation and cell-barrier injury during asthma by modulating miR-149. 11 According to the study of Austin et al, PTV1 was upregulated in the primary airway smooth muscle cells of patients with asthma and PVT1 expression might affect the proliferation of airway smooth muscle cells and the release of interleukin (IL)-6. 12 However, the expression of lncRNA PVT1 in the serum of BA patients and whether lncRNA PTV1 could be used for BA diagnosis and treatment require further investigation.…”