Experimental Lung Research最新文献

{"title":"Hypobaric hypoxia promotes the production of IL-10 of lung NKT cells in HAPE rats to fight inflammation.","authors":"Dewei Li, Chun Wang, Zhaoquan Su, Jiaxue Ma, Weina Kong, Lingling Dong, Xuemei Wei, Xiumin Ma","doi":"10.1080/01902148.2025.2515361","DOIUrl":"https://doi.org/10.1080/01902148.2025.2515361","url":null,"abstract":"<p><p><b>Background:</b> There are environment-dependent pro-inflammatory and anti-inflammatory pathways during exposure to high altitudes. Although inhibiting the inflammatory pathway can alleviate high altitude pulmonary edema (HAPE), it is currently unclear whether inflammation is the cause of edema or the result of edema in HAPE-afflicted patients. Natural killer T (NKT) cells are a subset of T cells that play an important role in a variety of lung diseases. However, its specific role in HAPE remains unclear. <b>Methods:</b> HAPE rat model was established under hypobaric hypoxia condition. To investigate the role of NKT cells in HAPE, phenotypic and functional changes of NKT cells and their subpopulations were analyzed by flow cytometry. To further investigate the effect of TNF-α on NKT cells, rats were given intraperitoneal injection of TNF-α, and then, NKT cells were characterized by flow cytometry. Subsequently, the levels of TNF-α in the lungs and spleens of rats were detected by ELISA, and HAPE rats were treated with curcumin. <b>Results:</b> Compared with normal control, the ratio of TNF-α and IL-10 secreted by lung NKT cells was decreased in HAPE rats induced by hypoxia. Further analysis showed that the mean fluorescence intensity (MFI) of TNF-α in NKT cells did not change significantly, but the MFI of IL-10 increased significantly. Moreover, the MFI of IL-10 produced by TNF-α-treated rat lung NKT cells was higher, which was completely different from spleen NKT cells. ELISA experiments indicated that TNF-α was enriched in the lung tissue of rats regardless of hypoxia, and the level of TNF-α in lung tissue was upregulated after hypoxia. Furthermore, when HAPE rats were treated with curcumin, the MFI of IL-10 in the NKT cell subsets decreased. <b>Conclusions:</b> NKT cells produce high levels of IL-10, which inhibits the production of lung inflammation in HAPE rats. With the increase of TNF-α level, the inhibitory effect of lung NKT cells on inflammation was further enhanced. When the level of TNF-α decreases, the anti-inflammatory effect of NKT cells also weakens accordingly. Hence, NKT cells play a protective role in HAPE rat lungs.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"51 1","pages":"38-49"},"PeriodicalIF":1.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PM2.5 induces ferroptosis in chronic obstructive pulmonary diseases <i>via</i> the GSK-3β/NRF2 pathway.","authors":"Dong Ye, Jie Ou, Dongshuang Zhu, Ge Bai, Meihua Guo, Xiaoting Zou, Ming Lei, Weifeng Zou","doi":"10.1080/01902148.2025.2536484","DOIUrl":"https://doi.org/10.1080/01902148.2025.2536484","url":null,"abstract":"<p><p><b>Background:</b> Recent studies have shown that fine particulate matter (PM2.5) exposure is a key harmful risk factor for chronic obstructive pulmonary disease (COPD) and PM2.5-associated ferroptosis plays an important role during the process of airway oxidative stress. Our preliminary study revealed that PM2.5 reduces the expression of phosphorylated glycogen synthase kinase (GSK)-3β in airway epithelial cells, the overactivity of the GSK-3β/Nuclear Factor erythroid 2-Related Factor 2 (NRF2) pathway is related to ferroptosis. Accordingly, we explored whether PM2.5 could induce ferroptosis in airway epithelial cells and promote the development of COPD <i>via</i> the GSK-3β/NRF2 pathway. <b>Methods:</b> The effect of GSK-3β/NRF2-mediated ferroptosis was assessed using an <i>in vivo</i> model of 20 μg/μl PM2.5-induced COPD by tracheal infusion and 50 μg/ml PM2.5-exposed airway epithelial cells <i>in vitro</i>. Then we performed qRT-PCR to detect mRNA expression; Western blotting, immunofluorescence and immunohistochemical staining to detect protein expression; flow cytometry and spectrophotometry to measure the levels of intracellular lipid peroxidation; small animal spirometry to examine the lung function in mouse, and hematoxylin and eosin (H&E) staining to measure the average alveolar septa in mouse lung sections. <b>Results:</b> We found that PM2.5 decreased the ferroptosis marker mRNA expression of NRF2, SLC7A11 and GPX4, and also decreased the protein expression of p-GSK-3β, NRF2, SLC7A11 and FTH-1, increased the protein expression of NCOA4, then increased the level of lipid peroxidation and MDA in human airway epithelial cells. Further, PM2.5 reduced the expression of p-GSK-3β, NRF2, SLC7A11 and GPX4 in the lungs, subsequently induced lung injury and impaired lung function of mice. Treatment with ferroptosis inhibitors FER-1 and GSK-3β inhibitor TDZD-8 reversed this effect. <b>Conclusion:</b> Our findings suggested that PM2.5 induced ferroptosis of airway epithelial cells, contributing to airway oxidative stress <i>via</i> the GSK-3β/NRF2 signaling pathway <i>in vivo</i> and <i>in vitro</i>, which could be a therapeutic target for PM2.5-induced COPD.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"51 1","pages":"79-92"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish as a model for investigating <i>Klebsiella pneumoniae</i>-driven lung injury and therapeutic targets.","authors":"Jian Ye, Lei Lu, Xiao-Hong Rui, Mei-di Ren, Fan Tu, Zhong-Bo Shang, Jun Liu","doi":"10.1080/01902148.2025.2472328","DOIUrl":"10.1080/01902148.2025.2472328","url":null,"abstract":"<p><p><b>Background:</b> Lung injury induced by Klebsiella pneumoniae infection presents a significant challenge, with complex molecular mechanisms driving tissue damage and immune dysregulation. This study aimed to establish a zebrafish model of K. pneumoniae-induced lung injury to explore the underlying molecular mechanisms involved in tissue damage, immune responses, and development.</p><p><p><b>Methods:</b> A zebrafish model was developed by injecting K. pneumoniae into the swim bladder at 96 h post-fertilization (hpf). The immune response, including neutrophil migration and cytokine secretion, was assessed through histological analysis and quantitative measures. Transcriptomic analysis was performed to evaluate gene expression changes related to lung development, immune regulation, and metabolism. The role of the TGF-β signaling pathway in immune response and tissue repair was investigated using the TGF-β inhibitor SB 431542.</p><p><p><b>Results:</b> Infection with K. pneumoniae induced rapid neutrophil migration and the secretion of inflammatory cytokines such as IL-6, IL-1β, TNF-α, and TNF-β, similar to immune responses seen in mouse models. Transcriptomic analysis revealed significant alterations in genes involved in lung development, immune responses, and metabolic pathways, underscoring the broad impact of infection on physiological regulation. The TGF-β signaling pathway was found to play a dual role: it promoted immune cell recruitment and cytokine secretion but suppressed developmental genes, delaying tissue repair. Treatment with SB 431542 reduced neutrophil aggregation, lowered cytokine levels, and restored gene expression related to development and repair.</p><p><p><b>Conclusions:</b> This zebrafish model effectively mimics K. pneumoniae-induced lung injury, offering valuable insights into the molecular mechanisms of tissue damage and immune dysregulation. Targeting the TGF-β signaling pathway holds therapeutic potential for reducing inflammation and promoting tissue repair, providing a foundation for the development of new treatment strategies for lung infections.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"51 1","pages":"11-22"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AIP4 inhibits NPE pulmonary microvascular endothelial cell apoptosis and barrier failure <i>via</i> regulation of TRPV4 subcellular location <i>in vitro</i>.","authors":"Mingbo Luo, Kaihua Yang, Yingtao Wu, Peng Wen, Qiao Ding","doi":"10.1080/01902148.2025.2526372","DOIUrl":"https://doi.org/10.1080/01902148.2025.2526372","url":null,"abstract":"<p><p><b>Background</b>: Neurogenic pulmonary edema (NPE) is a severe complication of subarachnoid hemorrhage that aggravates pulmonary microvascular endothelial barrier dysfunction. In this study, we aimed to explore the role of TRPV4 in NPE progression. <b>Method</b>: An NPE rat model was established through the endovascular perforation technique for the collection of NPE serum and pulmonary microvascular endothelial cells (PMVECs). PMVECs were incubated with NPE serum, the FITC-dextran extravasation was applied for permeability analysis, and the cell apoptosis was measured by flow cytometry. TRPV4 subcellular localization was detected by immunofluorescent staining. Finally, we performed the co-immunoprecipitation for AIP4 and TRPV4 binding association analysis. <b>Results</b>: NPE serum incubation promoted PMVECs apoptosis and barrier dysfunction. The TRPV4 level and p38 signaling were activated in PMVECs treated with NPE serum. However, these phenomena were reversed by TRPV4 inhibition. AIP4 promoted TRPV4 ubiquitination and led to the transfer of TRPV4 from the cell membrane to the cytoplasm. Overall, AIP4 ubiquitinated TRPV4, leading to p38 signaling inhibition, thereby blocking PMVECs apoptosis and barrier dysfunction under the NPE serum. <b>Conclusion</b>: TRPV4 is ubiquitinated by API4 and transferred to the cytoplasm, enhancing p38 signaling to promote PMVECs apoptosis and barrier dysfunction under NPE serum conditions.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"51 1","pages":"64-76"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>METTL14</i>/<i>YTHDF1</i> mediates m6A modification of <i>PTBP1</i> to regulate PDGF-BB-induced airway smooth muscle cell function.","authors":"Canming Qiu, Zhenzhu Liao, Pingping Guo, Jun Liu","doi":"10.1080/01902148.2025.2546817","DOIUrl":"https://doi.org/10.1080/01902148.2025.2546817","url":null,"abstract":"<p><strong>Background: </strong>Increased proliferation and migration of abnormal airway smooth muscle cells (ASMCs) are significantly associated with asthma. This study aimed to investigate the effects of methyltransferase-like 14 (<i>METTL14</i>), YTH domain-containing family Protein 1 (<i>YTHDF1</i>), and polypyrimidine tract-binding protein 1 (<i>PTBP1</i>) on platelet-derived growth factor-BB (PDGF-BB)-treated ASMCs.</p><p><strong>Methods: </strong>ASMCs were treated with PDGF-BB to mimic cell remodeling. A cell counting kit-8 (CCK-8) assay was performed to detect cell viability. Cell proliferation was detected by 5-Ethynyl-2'-deoxyuridine (EdU) assay. The migration and invasion of cells were measured by wound healing assay and transwell assay. Interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α) were evaluated using ELISA kits. The oxidative stress markers reactive oxygen species (ROS) and malondialdehyde (MDA) levels were evaluated using corresponding kits. RT-qPCR and western blotting were utilized to assess mRNA and protein expression. The m6A level was determined using methylated RNA immunoprecipitation (MeRIP) assay. RNA Immunoprecipitation (RIP) assay was used to evaluate the binding of <i>METTL14</i> or <i>YTHDF1</i> to <i>PTBP1</i> mRNA. The binding of <i>METTL14</i> to <i>PTBP1</i> was quantified by dual-luciferase assay.</p><p><strong>Results: </strong>PDGF-BB treatment promoted ASMCs proliferation, migration, invasion, secretion of IL-1β and TNF-α, increased MDA and ROS levels, and promoted macrophage polarization. Knockdown of <i>PTBP1</i> attenuated PDGF-BB-induced proliferation, migration, invasion, inflammation, oxidative stress, and macrophage polarization in ASMCs. <i>METTL14</i>/<i>YTHDF1</i> facilitated the m6A methylation modification of <i>PTBP1</i>. Elevated <i>PTBP1</i> expression nullified the influence of increased <i>METTL14</i> expression on PDGF-BB-stimulated ASMCs. <i>METTL14</i> influenced the expression of nuclear factor kappa B (NF-κB) pathway-associated proteins <i>via PTBP1</i>.</p><p><strong>Conclusion: </strong>The m6A methylation of <i>PTBP1</i>, mediated by <i>METTL14</i>/<i>YTHDF1</i>, played a critical role in modulating the functional behavior of ASMCs induced by PDGF-BB during the progression of asthma.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"51 1","pages":"64-78"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening and validation of stable housekeeping genes in lung organoids and rat lung models under tobacco exposure.","authors":"Yi Liu, Jing Zhang, Xi Fang, Guang Cheng, ChengHao Luo, Yuanjing Huang, Long Huang","doi":"10.1080/01902148.2025.2554368","DOIUrl":"https://doi.org/10.1080/01902148.2025.2554368","url":null,"abstract":"<p><p>In recent years, with the increasing severity of air pollution and environmental degradation, research on lung-related diseases has become more intensive. Lung organoids, as 3D <i>in vitro</i> culture models, can simulate the local microenvironment and physiological functions of lung tissue and are widely used in studies on the development and mechanisms of lung-related diseases. However, the precise application of lung organoids is still in the developmental stage, particularly regarding the screening and validation of stable housekeeping genes in lung organoids, which remains unclear. This study utilized human/mouse-derived lung organoids and rat lung tissue as research subjects. By establishing physiological, traditional cigarette, and heated cigarette exposure models and combining BestKeeper, GeNorm, and NormFinder software, the expression stability of various housekeeping genes under different research subjects and exposure models was analyzed to identify stable housekeeping genes for lung-related research. The results showed that in human/mouse-derived lung organoids and rat lung tissue, the baseline expression levels of housekeeping genes were generally high. Among them, GAPDH exhibited the highest expression stability and was least affected by exposure environments, followed by β-actin, RPS16, and RPL19, while 18s showed relatively poor stability. Furthermore, when using a stable single housekeeping gene (e.g., GAPDH) for relative quantification of target gene expression, the experimental results were more significant. When GAPDH and β-actin were used as combined housekeeping genes for target gene quantification, the changes in target gene expression were more pronounced, with stronger statistical significance. In conclusion, this study provides stable single housekeeping genes (GAPDH) and combined housekeeping genes (GAPDH + β-actin) for lung organoid research, contributing to further advancements in the study of lung health.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"51 1","pages":"79-94"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nasal mucosa-derived ecto-mesenchymal stem cells ameliorate LPS-induced acute lung injury.","authors":"Yifei Yang, Junguo Chen, Jiaojiao Chen, Xuelei Gong, Wen Xiang, Xun Wang, Naiyan Lu, Xiaoli Ge","doi":"10.1080/01902148.2025.2558686","DOIUrl":"10.1080/01902148.2025.2558686","url":null,"abstract":"<p><p>Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with significant morbidity and mortality rates. Mesenchymal stem cells (MSCs) derived from nasal mucosa, known as EMSCs, have demonstrated therapeutic potential in conditions such as liver failure and bone defects. However, investigations focusing on the application of EMSCs in ALI are still lacking. In our study, an ALI model was induced in rats through lipopolysaccharide (LPS) administration, with subsequent intravenous delivery of either saline or EMSCs. Co-culture experiments using transwell systems revealed that EMSCs improved the viability and proliferation of A549 cells, while also suppressing LPS-induced inflammation and apoptosis. Moreover, the administration of EMSCs not only improved pulmonary microvascular permeability and alleviated histopathological damage, but also exerted downregulatory effects on the levels of pro-inflammatory cytokines, including TNFα, IL6, and IL-1β, while concurrently upregulating the expression of anti-inflammatory cytokine IL-10 in both bronchoalveolar lavage fluid (BALF) and plasma. Immunohistochemistry analysis further revealed an elevated expression of proliferation marker Ki67 and anti-apoptotic protein Bcl2, accompanied by a reduction in the expression of pro-apoptotic protein Bax, thus indicating the beneficial outcomes of EMSCs. Collectively, these findings underscore the potential of EMSC-based therapies as promising and effective strategies for the treatment of lung injury.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"51 1","pages":"95-109"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP4-mediated deubiquitination of SRC-1 regulates macrophage polarization and asthma inflammation.","authors":"Lina Yan, Yun Shen, Jing Song, Liang Liu, Zhuang Ma","doi":"10.1080/01902148.2025.2506373","DOIUrl":"10.1080/01902148.2025.2506373","url":null,"abstract":"<p><p><b>Background:</b> Asthma, the most common chronic respiratory disorder affecting individuals of all ages, is driven by inflammation that leads to airway hyperresponsiveness, airway wall remodeling, and mucus production. While inhaled corticosteroids remain the primary treatment despite their limitations, further research into the molecular mechanisms of asthma is needed to identify new therapeutic targets. <b>Methods:</b> A mouse model of asthma was created by treating mice with OVA. HE and PAS staining were used to detect histopathology. Gene and protein expression levels were assessed using qPCR, Western blot, and ELISA. The relationship between USP4 and SRC-1 was examined using Co-IP assay. The ubiquitination levels of SRC-1 were detected using IP assay while macrophage polarization was analyzed by flow cytometry. <b>Results:</b> The ovalbumin-induced mouse model of asthma exhibited a large quantity of inflammatory cell infiltration, proliferation of goblet cells, and increased mucus secretion. SRC-1 expression was upregulated in an OVA-induced mouse model of asthma. Downregulation of SRC-1 reduced macrophage polarization to the M1 phenotype, protecting against OVA-induced asthma, whereas SRC-1 overexpression inhibited M2 macrophage polarization by suppressing the NF-kB signaling pathway. Furthermore, USP4 was found to deubiquitinate SRC-1, enhancing its protein stability. The regulatory axis between USP4 and SRC-1 was validated <i>in vivo.</i> <b>Conclusion:</b> This study demonstrates that USP4 regulates the deubiquitination of SRC-1, which inhibits M2 macrophage polarization and reduces asthma-related inflammation. These findings suggest that USP4 and SRC-1 may serve as potential therapeutic targets for asthma treatment.HighlightsSRC-1 is upregulated in OVA-induced asthma and correlated to macrophage.SRC-1 knockdown reduces M1 macrophage polarization and airway inflammation in the asthma model.SRC-1 overexpression or USP4 overexpression suppresses IL-4-induced M2 polarization via the NF-κB pathway.USP4 regulates the deubiquitination of SRC-1, influencing macrophage polarization and inflammation.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"51 1","pages":"50-63"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Store-operated Ca²⁺ entry contributes to the ASM phenotype transition in asthma.","authors":"Hangqi Ni, Ting Li, Junjun Chen, Yuying Wei, Mengling Xia, Qing Wang","doi":"10.1080/01902148.2025.2486951","DOIUrl":"https://doi.org/10.1080/01902148.2025.2486951","url":null,"abstract":"<p><strong>Aim of the study: </strong>Phenotype modulation of airway smooth muscle cells (ASMC), characterized by a shift toward a more proliferative and synthetic phenotype from contractile cells, plays a crucial role in airway remodeling in asthma. STIM1 and Orai1, key components of store-operated Ca²⁺ entry (SOCE), have been demonstrated to enhance ASMC proliferation and migration. This study investigated the impact of STIM1/Orai1-mediated SOCE on ASMC phenotype transition and extracellular matrix (ECM) deposition in asthma.</p><p><strong>Materials and methods: </strong>The ASMCs were treated with PDGF-BB and SOCE inhibitors. Immunocytochemistry staining, enzyme-linked immunosorbent assay, and western blot assay were employed to detect the ASMC's proliferation as well as the expressions of contractile proteins, inflammatory cytokines and ECM. Moreover, the effect of SOCE repression in ECM deposition were evaluated in an asthmatic mouse model.</p><p><strong>Results: </strong>ASMCs from airways of mice were treated with PDGF-BB to induce the 'proliferative/synthetic' phenotype. We observed elevated expressions of STIM1 and Orai1 in phenotype-switched ASMCs, along with enhanced SOCE. SKF-96365 and RO2959, which target of STIM1/Orai1, could significantly inhibit SOCE activation in ASMCs. Moreover, these SOCE inhibitors mitigated the elevated proliferation rate, decreased the secretion of inflammatory cytokines and restored the reduced levels of contractile proteins in phenotype-switched ASMCs induced by PDGF-BB. Furthermore, we observed that PDGF-BB-induced 'proliferative/synthetic' ASMCs exhibited increased production of ECM components, including collagen I and fibronectin, as well as metalloproteinases (MMPs) such as MMP2 and MMP9, all of which were effectively inhibited by SKF-96365 and RO2959. <i>In vivo</i> experiments also demonstrated that SOCE inhibitors decreased ECM deposition and MMPs production in the asthmatic mouse model.</p><p><strong>Conclusions: </strong>These findings underscored the significant role of STIM1/Orai1-mediated SOCE in ASMC phenotype modulation and its impact on the excessive ECM deposition driven by ASMCs. Thus, our findings suggest that STIM1/Orai1-mediated SOCE may contribute to airway remodeling in asthma.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"51 1","pages":"23-37"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of PRDX6 in the protective role of MANF in acute lung injury in rats.","authors":"Xiuli Yang, Xueying Xiao, Leiying Zhou, Yujun Shen, Lixia Wang, Qiying Shen","doi":"10.1080/01902148.2025.2454032","DOIUrl":"10.1080/01902148.2025.2454032","url":null,"abstract":"<p><p><b>Aim/Purpose of the study:</b> Acute lung injury (ALI) is a severe respiratory disease with high mortality, mainly due to overactivated oxidative stress and subsequent pyroptosis. Mesencephalic astrocyte-derived neurotrophic factor (MANF), an inducible secretory endoplasmic reticulum (ER) stress protein, inhibits lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the exact molecular mechanism remains unclear. Peroxiredoxin 6 (PRDX6), a peroxidase with a dual enzymatic function, is essential in regulating oxidative stress, which is closely associated with ALI. Furthermore, PRDX6 is an interacting protein of MANF. Therefore, this study aims to investigate the role of PRDX6 in the protective effect of MANF on ALI.</p><p><p><b>Materials and Methods:</b> In this study, we used LPS to establish the LPS-induced ALI model. Recombinant human MANF was administrated to wide-type (WT) and PRDX6 knockout (PRDX6^-/-) rats.</p><p><p><b>Results:</b> In WT rats, MANF reversed the increases of PRDX6, ROS overgeneration, and pyroptosis-related protein-Gasdermin D (GSDMD) induced by LPS challenge. In PRDX6^-/- rats, ROS generation, the protein level of GSDMD-N, and lung injury were not significantly decreased after human recombinant MANF administration in LPS-induced ALI.</p><p><p><b>Conclusions:</b> PRDX6 is involved in the protective role of MANF on ALI. It is a key target molecule for MANF to exert ALI inhibitory effects.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"51 1","pages":"1-10"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}