Effects of 1,25-Dihydroxyvitamin D3 on the Prevention of Chronic Obstructive Pulmonary Disease (COPD) in Rats Exposed to Air Pollutant Particles Less than 2.5 Micrometers in Diameter (PM2.5)

Chen, Lerong; Yuan, Xiaolan; Zou, Luru; Peng, Jian-Ping; Hu, Xinchun

doi:10.12659/msm.905509

Cited by 11 publications

(7 citation statements)

References 22 publications

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“…A phase 2 clinical experimental study showed that inhibiting JNK reduced pulmonary fibrosis in patients ( 20 ). As previously reported, the activation of NF-κB ( 21 ) and inflammatory factor secretion mediated by PM2.5 ( 22 ) could be blocked by a JNK inhibitor, and Wnt5a suppression abrogated the PM2.5-mediated increase in inflammatory cytokines in HBECs. We further demonstrated that PM2.5 increased the levels of phosphorylated JNK and NF-κB, resulting in inflammatory factor secretion and collagen production by ASMCs, which was contrary to the application effect of BOX5 (a specific Wnt5a antagonist) or Wnt5a siRNA.…”

Section: Discussionsupporting

confidence: 62%

PM2.5 induces lung inflammation and fibrosis via airway smooth muscle cell expression of the Wnt5a/JNK pathway

Zou,

Liu,

et al. 2023

J Thorac Dis

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Background In recent years, particulate matter 2.5 (PM2.5) exposure has been considered a key dangerous factor in chronic obstructive pulmonary disease (COPD). The dysfunction of airway smooth muscle cells (ASMCs) facilitates lung inflammation and fibrosis in COPD. Therefore, we explored whether PM2.5 could promote the inflammatory response and fibrosis in ASMCs in vivo and in vitro via the wingless-related integration site 5a (Wnt5a)/c-Jun N-terminal kinase (JNK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Methods Wnt5a expression in the bronchoalveolar lavage fluid (BALF) of COPD patients exposed to PM2.5 was measured by enzyme-linked immunosorbent assay (ELISA). Mice were intratracheally injected with PM2.5 and a Wnt5a antagonist (BOX5). ASMCs were transfected with Wnt5a small interfering RNA (siRNA), BOX5 and the JNK inhibitor SP600125 before PM2.5 stimulation. Hematoxylin and eosin (H&E) staining was performed to measure the inflammatory response and airway fibrosis. The production of Wnt5a/JNK/NF-KB pathway factors was analyzed by Western blotting. The secretion of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α) was measured by ELISA. The expression levels of alpha smooth muscle actin (α-SMA), collagen I and collagen III were assessed by quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting. Results We found that the increase in Wnt5a expression in the BALF of COPD patients was positively correlated with the levels of PM2.5 exposure. The Wnt5a/JNK/NF-κB pathway was activated in the lung samples of PM2.5-induced model mice and PM2.5-exposed ASMCs, which promoted the production of α-SMA, collagen I and collagen III and increased the secretion of IL-6, IL-8 and TNF-α. Furthermore, our results showed that BOX5 could prevent these effects. Wnt5a siRNA blocked the activation of the Wnt5a/JNK/NF-κB pathway and inhibited the effects of PM2.5 on fibrosis and inflammation in ASMCs. SP600125 blocked the phosphorylation of NF-κB and inhibited inflammation and fibrosis in PM2.5-exposed ASMCs. Conclusions These findings suggest that PM2.5 stimulation of ASMCs induces pulmonary inflammatory factor expression and collagen deposition during COPD via the Wnt5a/JNK pathway, which indicates that modulating the Wnt5a/JNK pathway could be a promising therapeutic strategy for PM2.5-induced COPD.

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Section: Discussionsupporting

confidence: 62%

PM2.5 induces lung inflammation and fibrosis via airway smooth muscle cell expression of the Wnt5a/JNK pathway

Zou,

Liu,

et al. 2023

J Thorac Dis

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“…Therefore, vitamin D has been of interest for the potential treatment and prevention of various diseases, such as chronic kidney disease and cystic fibrosis ( 65-67 ). In a previous in vivo study, vitamin D3 supplementation was found to alleviate lung injury in rats with COPD whilst also reducing cell apoptosis in the lung tissues ( 68 ). Clinical studies have also shown that vitamin D3 supplementation can alleviate moderate or severe COPD to reduce the incidence of upper respiratory tract infections ( 23-69 ).…”

Section: Discussionmentioning

confidence: 96%

Vitamin D3 alleviates cigarette smoke extract‑mediated epithelial‑mesenchymal transition and fibrogenesis by upregulating CC16 expression in bronchial epithelial cells

Mao

Feng

2022

Exp Ther Med

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Vitamin D3 supplementation has been previously reported to inhibit the occurrence and development of chronic obstructive pulmonary disease (COPD). However, the underlying mechanism remains unclear. Epithelial-mesenchymal transition (EMT) and fibrogenesis have been associated with the development of COPD. The aim of the present study was to investigate the potential effects and mechanism of vitamin D3 in an in vitro model of cigarette smoke (CS)-induced EMT and fibrosis, with specific focus on the role of club cell protein 16 (CC16). CS extract (CSE) at different concentrations (5, 10 and 20%) was used to treat 16-HBE cells to induce EMT and fibrogenesis following which they were treated with vitamin D3. Subsequently, the 20% CSE group was selected for further experiments, where 16-HBE cells were divided into the following five groups: The control group; the CSE group; the low-dose vitamin D3 group (250 nM); the medium-dose vitamin D3 group (500 nM); and the high-dose vitamin D3 group (1,000 nM). Western blot analysis was used to detect the protein expression levels of the EMT-related proteins E-cadherin, N-cadherin, Slug and α-SMA, fibrogenesis-related proteins collagen Ⅳ and fibronectin 1, proteins involved in the TGF-β1/SMAD3 signaling pathway and CC16. Immunofluorescence was used to measure the protein expression levels of E-cadherin, N-cadherin and collagen Ⅳ. Specific CC16 knockdown was performed using short hairpin RNA transfection to investigate the role of CC16. The results of the present study found that vitamin D3 could increase the protein expression level of CC16 to inhibit the activation of the TGF-β1/SMAD3 signaling pathway; thereby reducing the 20% increase in CSE-induced EMT- and fibrogenesis-related protein expression levels. Following CC16 knockdown, the inhibitory effects of vitamin D3 on EMT- and fibrogenesis-related protein expression were partially reversed. To conclude, these results suggest that vitamin D3 can inhibit the protein expression levels of EMT- and fibrogenesis-related proteins induced by CSE, at least partially through the function of CC16. These findings are expected to provide novel theoretical foundations and ideas for the pathogenesis and treatment of COPD.

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“…Epidemiological and genetic risk factors for COPD include long-term smoking, persistent exposure to air pollution, respiratory infections, inhalation of biofuel smoke and occupational dust ( 24 ). Among them, smoking is a pivotal risk factor, significantly contributing to the development of COPD, thus increasing the rate of impaired lung function ( 25 , 26 ).…”

Section: Discussionmentioning

confidence: 99%

Fucoxanthin ameliorates oxidative injury and inflammation of human bronchial epithelial cells induced by cigarette smoke extract via the PPARγ/NF‑κB signaling pathway

Chen

Zhu

2022

Exp Ther Med

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Chronic obstructive pulmonary disease (COPD) is a prevalent and long-term airway disease. It has been reported that fucoxanthin (FX) exhibits anti-inflammatory and antioxidant effects. However, the underlying mechanism of FX in COPD remains unknown. Therefore, to investigate the effect of FX on COPD, BEAS-2B cells were treated with cigarette smoke extract (CSE). The viability of BEAS-2B cells treated with increasing doses of FX was assessed by Cell Counting Kit-8. Lactate dehydrogenase (LDH) levels were measured using a corresponding kit. In addition, ELISA was carried out to detect the content of TNF-α, IL-1β and IL-6. Additionally, a TUNEL assay and western blot analysis were performed to assess the cell apoptosis rate. Furthermore, 2' ,7'-dichlorodihydrofluorescein diacetate was used to measure reactive oxygen species levels, while the contents of oxidative stress-associated indexes were determined using the corresponding kits. Bioinformatics analysis using the search tool for interactions of chemicals database predicted that peroxisome proliferator-activated receptor γ (PPARγ) may be a target of FX. The binding capacity of FTX with PPARγ was confirmed by molecular docking. The protein expression levels of the PPARγ/NF-κB signaling-associated factors were detected by western blot analysis. Finally, the regulatory mechanism of FX in COPD was revealed following cell treatment with the PPARγ inhibitor, T0070907. The results demonstrated that FX enhanced CSE-induced BEAS-2B cell viability and attenuated CSE-induced BEAS-2B cell inflammation and oxidative damage, possibly via triggering PPARγ/NF-κB signaling. Pre-treatment of BEAS-2B cells with the PPARγ inhibitor, T0070907, could reverse the protective effects of FX on CSE-induced BEAS-2B cells. Overall, the present study suggested that FX could ameliorate oxidative damage as well as inflammation in CSE-treated human bronchial epithelial in patients with COPD via modulating the PPARγ/NF-κB signaling pathway.

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Effects of 1,25-Dihydroxyvitamin D3 on the Prevention of Chronic Obstructive Pulmonary Disease (COPD) in Rats Exposed to Air Pollutant Particles Less than 2.5 Micrometers in Diameter (PM2.5)

Cited by 11 publications

References 22 publications

PM2.5 induces lung inflammation and fibrosis via airway smooth muscle cell expression of the Wnt5a/JNK pathway

PM2.5 induces lung inflammation and fibrosis via airway smooth muscle cell expression of the Wnt5a/JNK pathway

Vitamin D3 alleviates cigarette smoke extract‑mediated epithelial‑mesenchymal transition and fibrogenesis by upregulating CC16 expression in bronchial epithelial cells

Fucoxanthin ameliorates oxidative injury and inflammation of human bronchial epithelial cells induced by cigarette smoke extract via the PPARγ/NF‑κB signaling pathway

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