The aim of the present study was to investigate the impact of N‑acetylcysteine (NAC) on the expression of reduced nicotinamide adenine dinucleotide phosphate oxidase 1 (Nox1), and the proliferation and apoptosis of pulmonary artery smooth muscle cells (PASMCs) in rats exhibiting monocrotaline (MCT)‑induced pulmonary hypertension, and to investigate the possible mechanisms and treatment roles of NAC in pulmonary vascular remodeling (PVR). A total of 18 Wistar rats were randomly divided into three groups: The control (C) group; the MCT (M) group; and the NAC (N) group. The right ventricular hypertrophy index (RVHI) and other indicators were recorded 6 weeks subsequently. Groups C and M were divided into two subgroups: Groups C1 and M1 (control); and group C2 and M2 group (treated with ML171). Group N was not sub‑divided. PASMCs were isolated, and the vascular remodeling and Nox1 positioning were observed. The expression of Nox mRNA in each group, and the proliferation, apoptosis, and superoxide dismutase (SOD) activity of PASMCs, prior to and following the ML171 treatment, were measured. NAC was able to decrease RVHI and other indicators (P<0.001). The mRNA expression of Nox1 and Nox4 in group M was significantly increased compared with group C (P<0.05), and NAC was able to significantly decrease the expression of these two factors in lung tissue (P<0.001). MCT‑PASMCs exhibited differences in Nox1 mRNA expression (P<0.001), and the total SOD activity was Nox1‑dependently increased (r=0.949; P<0.001). NAC was able to decrease Nox1‑derived reactive oxygen species in PASMCs, thereby improving PVR. Nox1 was able to increase SOD activity, thereby demonstrating its positive effect on the proliferation of MCT‑PASMCs.
The present study investigated the intervention efficacies of rosiglitazone (ROS) and retinoin (RET) on bleomycin-induced pulmonary fibrosis in rats. A total of 48 rats were randomly divided into the control group (group C), the model group (group M), the dexamethasone group (group D), the ROS group (group R), the RET group (group W) and the ROS + RET group (group L). Group M and the treatment groups were intratracheally injected with 5 mg/kg bleomycin, while group C was injected with saline. The lungs of rats in each group were inspected using high resolution computed tomography (HRCT), lung tissue hematoxylin and eosin staining and Masson staining; furthermore, lung L-hydroxyproline (Hyp) content and the concentration of transforming growth factor β1 (TGF-β1) serum of each group were also determined. The fibrosis score, Hyp content and TGF-β1 concentration of each treatment group were significantly lower when compared with group M (P<0.01), while the imaging results were improved when compared with group M, with lower alveolitis and fibrosis scores. Group L, R and W exhibited significantly lower fibrosis scores, Hyp content and TGF-β1 concentrations when compared with group D (P<0.05). Imaging results for group L, R and W indicated that while the imaging results were superior to group D, group L was lower than groups R and W (P<0.05). No significant difference in the fibrosis score, Hyp content and TGF-β1 concentration was exhibited between groups R and W (P>0.05). Findings from the present study conclude that ROS and RET are able to suppress bleomycin-induced pulmonary fibrosis with improved efficacies when compared with dexamethasone; furthermore, the combination of these two pharmacological agents may exert synergistic effects.
The aims of the present study were to elucidate the regulatory effect of exogenous Tribbles homologue 3 (TrB3) expression on the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition (eMT) in transforming growth factor-β1 (TGF-β1)-induced mouse alveolar epithelial cells (Mle-12) and investigate the underlying regulatory mechanisms. TrB3 expression was upregulated and downregulated using gene overexpression and rna interference techniques, respectively. TGF-β1-stimulated Mle-12 cells were examined for eMT and activation condition of the Wnt/β-catenin signaling pathway using cell counting Kit-8, flow cytometry, western blotting, reverse transcription-quantitative Pcr, eliSa and immunofluorescence techniques. during TGF-β1-induced eMT, TrB3 expression was found to be significantly upregulated (P<0.05). In the TRB3 overexpression group, upregulated expression of β-catenin and EMT-related genes and proteins was observed (P<0.05), and an increase in fibrosis-related factors in the cell culture supernatant was detected (P<0.05); however, the results were the opposite in the TRB3 downregulated group (P<0.05). TRB3 may be involved in the regulation of eMT in TGF-β1-induced Mle-12 cells through the Wnt/β-catenin signaling pathway.
The aim of the present study was to investigate whether the expression of tribbles pseudokinase 3 (TRB3) is involved in pulmonary interstitial fibrosis and to examine the possible mechanisms. The expression of TRB3 in murine alveolar type II epithelial cells (MLE-12 cells) following transforming growth factor β1 (TGF-β1) stimulation was assessed using various techniques, including western blot and reverse transcription-quantitative polymerase chain reaction assays. TRB3 overexpression and downregulation models were used to evaluate the impact of TRB3 on the TGF-β1-induced epithelial-mesenchymal transition (EMT) of MLE-12 cells. The downregulation of TRB3 was induced by RNA interference. The expression of TRB3 was significantly increased in MLE-12 cells following the activation of TGF-β1 (P<0.05). The overexpression of TRB3 was found to promote activation of the TGF-β1/Smad3 signaling pathway, EMT, and the upregulated expression of β-catenin and EMT-related genes and proteins (P<0.05), whereas the downregulation of TRB3 attenuated the promoting effect on EMT induced by TGF-β1. In addition, the overexpression of TRB3 inhibited MLE-12 cell proliferation by stimulating apoptosis, leading to the formation of pulmonary fibrosis (PF). The positive feedback loop demonstrated that TGF-β1 induced the expression of TRB3, and TRB3, in turn, stimulated EMT and promoted the onset of PF through activation of the TGF-β1/Smad3 signaling pathway. Therefore, TRB3 may promote the formation of PF through the TGF-β1/Smad3 signaling pathway.
The upregulation of TLR-4 in the pulmonary arterial smooth muscle cells of COPD patients could promote the inflammations and the MMP-9 expression, thus causing abnormal degradation of extracellular matrix, so it played an important role in the process of PVR.
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