Identification of circular RNA circVPS33A as a modulator in house dust mite-induced injury in human bronchial epithelial cells.

BACKGROUND: House dust mite has been well documented as a major source of allergen in asthma. Circular RNAs (circRNAs) vacuolar protein sorting 33A (circVPS33A, circ_0000455) is overexpressed in a murine asthma model. Herein, we sought to identify its critical action in Dermatophagoides pteronyssinus peptidase 1 (Der p1)-induced dysfunction of BEAS-2B cells. METHODS: The levels of circVPS33A, microRNA (miR)-192-5p, and high-mobility group box 1 (HMGB1) were assessed by quantitative real-time PCR (qRT-PCR) or western blot. Actinomycin D treatment and Ribonuclease R (RNase R) assay were used to characterize circVPS33A. Cell viability, proliferation, apoptosis, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and transwell assays, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to quantify interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and IL-6. Direct relationship between miR-192-5p and circVPS33A or HMGB1 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assay. RESULTS: CircVPS33A was highly expressed in asthma plasma and Der p1-treated BEAS-2B cells. Knocking down circVPS33A suppressed Der p1-induced injury in BEAS-2B cells. CircVPS33A targeted miR-192-5p. MiR-192-5p directly targeted HMGB1, and miR-192-5p-mediated repression of HMGB1 alleviated Der p1-driven cell injury. Furthermore, circVPS33A modulated HMGB1 expression through miR-192-5p. CONCLUSION: Our findings demonstrated that circVPS33A regulated house dust mite-induced injury in human bronchial epithelial cells at least partially depending on the modulation of the miR-192-5p/HMGB1 axis.

Effects of an early intervention using human amniotic epithelial cells in a COPD rat model.

The study aimed to investigate the effect of an early intervention using human amniotic epithelial cell (hAEC) in a rat model of chronic obstructive pulmonary disease (COPD). Twenty-four specific pathogen-free Wistar rats were randomized to the control, COPD, and COPD+hAEC groups. COPD was established by intratracheal LPS injection combined with smoke fumigation over 30days. On the first day of model establishment rats in the AEC group also received intratracheal instillation of 500,000 hAECs isolated from the placenta of healthy donors. The mean linear intercept (MLI) and mean alveolar number (MAN) were used to assess the degree of lung emphysema. IL-8 was measured using a radioimmunoassay, surfactant protein D (SP-D) was measured by ELISA, and matrix metalloproteinase (MMP)2 and MMP8 expression was assessed by PCR. Smoke fumigation combined to LPS injection successfully established a COPD rat model with significant emphysema and airway inflammation, elevated MLI and MAN, elevated systemic and lung tissue levels of IL-8 and SP-D (P<0.05), and high expression of MMP2 and MMP8. Rats in the COPD+hAEC group exhibited alleviated lung damage, MLI and MAN (P<0.05), reduced systemic and lung tissue levels of IL-8 and SP-D (P<0.05) and MMP2 and MMP8 expression (P<0.05). Early intervention using hAECs could delay disease progression in rats with COPD.