Experimental Lung Research最新文献

{"title":"Insulin-like growth factor-1 reduces hyperoxia-induced lung inflammation and oxidative stress and inhibits cell apoptosis through PERK/eIF2α/ATF4/CHOP signaling.","authors":"Haixia Cui,&nbsp;Shujian Zhang,&nbsp;Zhengxie Wu,&nbsp;Chunhua Xu,&nbsp;Dongyuan Xu,&nbsp;Zhengyong Jin","doi":"10.1080/01902148.2022.2106388","DOIUrl":"https://doi.org/10.1080/01902148.2022.2106388","url":null,"abstract":"<p><p><b>Background:</b> Insulin-like growth factor-1 (IGF-1), a member of the insulin family, has a high degree of homology with insulin and exhibits anti-inflammatory and anti-oxidative stress properties. However, the potential protective effect of IGF-1 on hyperoxia-induced lung injury remains unknown. In this study, we aimed to explore the effects and mechanism of action of IGF-1 in hyperoxia-induced lung injury in neonatal rats. <b>Materials and Methods:</b> Hematoxylin-eosin staining was used to observe pathological changes in lung tissue; transmission electron microscopy was used to examine the ultrastructure, and ELISA was used to detect the level of pro-inflammatory cytokines in bronchoalveolar lavage fluid. Further, malondialdehyde, glutathione, and superoxide dismutase activities in lung tissue were evaluated. TUNEL staining was used to detect cell apoptosis, and western blot analysis was used to detect the expression of Bax, Bcl-2, Caspase-3, p-PERK, p-eIF2α, ATF4, and CHOP in the lung tissue. Moreover, the wet/dry weight ratio of lung tissue was determined. <b>Results:</b> Intraperitoneal injection of IGF-1 effectively reduced lung tissue damage induced by hyperoxia; production of inflammatory cells and release of pro-inflammatory cytokines, oxidative stress, and cell apoptosis. Further, IGF-1 down-regulated the expression of ATF4, CHOP, and Bax/Bcl-2, and inhibited the phosphorylation of PERK and eIF2α. <b>Conclusion:</b> The results suggest that IGF-1 reduces hyperoxia-induced lung inflammation and oxidative stress in neonatal rats through the PERK/eIF2α/ATF4/CHOP signaling pathway and inhibits cell apoptosis.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":" ","pages":"187-197"},"PeriodicalIF":1.7,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40583131","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":"Collagen 3D matrices as a model for the study of cell behavior in pulmonary fibrosis","authors":"C. Machahua, V. Vicens-Zygmunt, Jesús Ríos-Martín, R. Llatjós, Ignacio Escobar-Campuzano, M. Molina-Molina, A. Montes-Worboys","doi":"10.1080/01902148.2022.2067265","DOIUrl":"https://doi.org/10.1080/01902148.2022.2067265","url":null,"abstract":"Abstract Purpose: Idiopathic pulmonary fibrosis (IPF) is a complex progressive chronic lung disease where epithelial to mesenchymal interaction, extracellular matrix (ECM) contact, and pro-fibrotic cytokines dynamics take part in the development of the disease. The study of IPF in the widespread in vitro two-dimensional (2 D) culture fails to explain the interaction of cells with the changing environment that occurs in fibrotic lung tissue. A three-dimensional (3 D) co-culture model might shed light on the pathogenesis of IPF by mimicking the fibrotic environment. Materials and Methods: Fibroblasts from nine IPF were isolated and embedded in collagen matrices with the alveolar epithelial human cell line (A549) on the top. Cells were also cultured in 2 D with and without TGF-β1 as a conventional model to compare with. Both types of cells were isolated separately. Protein and gene expression of the main fibrotic markers were measured by qPCR, Western blot, and ELISA. Results: IPF fibroblasts to myofibroblasts differentiation was observed in the 3 D model and in cells stimulated with TGF-β1. In addition, ECM-related genes were highly up-regulated in the 3 D collagen matrix. A549 co-cultured 3 D with IPF fibroblasts showed EMT activation, with down-regulation of E-cadherin (CDH1). However, other pro-fibrotic genes as VIM, TGFB1, and MMP7 were up-regulated in A549 co-cultured 3 D with fibroblasts. Conclusions: 3 D-collagen matrices might induce fibroblasts’ fibrotic phenotype as in the classic TGF-β1 model, by up-regulating genes associated with matrix production. In addition, IPF lung fibroblasts seem to exert a pro-fibrotic influence in A549 cells when they are co-cultured. These results suggest that an improved 3 D co-culture model might serve as an important tool to study the fibrotic process and its regulation.","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"48 1","pages":"126 - 136"},"PeriodicalIF":1.7,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48448168","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":"Effects of sulfur dioxide, ozone, and ambient air pollution on lung histopathology, oxidative-stress biomarkers, and apoptosis-related gene expressions in rats","authors":"S. Kheirouri, D. Shanehbandi, M. Khordadmehr, M. Alizadeh, Fateme Eskandari Vaezi, Razieh Musapour Sultan Abad, M. Mesgari-Abbasi","doi":"10.1080/01902148.2022.2072977","DOIUrl":"https://doi.org/10.1080/01902148.2022.2072977","url":null,"abstract":"Abstract Purpose of the Study Ambient air pollution (AAP) has become an important health problem globally. Besides, several pieces of evidence indicate that air pollutants such as sulfur dioxide (SO2) and ozone (O3) are major contributors to a wide range of non-communicable diseases. The present study investigated the effects of AAP, sulfur dioxide, and ozone on oxidative stress, histopathology, and some apoptosis-related genes expressions of lung tissue in a rat model. Materials and Methods Thirty-two Wistar rats were randomly divided into the control, AAP, sulfur dioxide (10 ppm), and ozone (0.6 ppm) groups. After five consecutive weeks’ exposure to the selected pollutants (3 h/day), lung tissues were harvested and immediately fixed with formalin. The samples were routinely processed, sectioned, stained with hematoxylin and eosin (H&E), and finally assessed for presence of pathological changes. Expression changes of BAX, p-53, EGFR, caspase-3, caspase-8 and caspase-9 were assayed using the RT-qPCR method. One hundred milligrams of lung tissues were extracted and the supernatants were used for assaying malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase activities. Results GPx activity was increased in the ozone (P = 0.05) and AAP (P < 0.001) groups and also MDA level in sulfur dioxide group (P = 0.008). Pathological lesions were mild, moderate, and severe in the sulfur dioxide, ozone, and AAP groups, respectively, as compared to control group (P ˂ 0.05). Exposure to AAP and sulfur dioxide enhanced BAX (P = 0.002) and caspase-8 (P < 0.001) mRNA expression, respectively. Caspases-3 and −8 mRNA expressions were elevated in ozone group (P < 0.001). Conclusions The results indicated induction of oxidative stress. Our results suggest the apoptosis stimuli effect of AAP and also the extrinsic apoptotic pathway trigger effect of sulfur dioxide and ozone in the lung tissue in the concentrations used in the present study. The histopathological and the genes expression changes may be a result of the induced oxidative stress in the lung tissues.","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"48 1","pages":"137 - 148"},"PeriodicalIF":1.7,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45655187","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":"3,3′-Diindolylmethane attenuates inflammation and fibrosis in radiation-induced lung injury by regulating NF-κB/TGF-β/Smad signaling pathways","authors":"Xia Zhou, Wu-an Bao, Xiangyu Zhu, Juan Lin, Junzhao Fan, Yang Yang, Xiang-Hui Du, Yue Wang","doi":"10.1080/01902148.2022.2052208","DOIUrl":"https://doi.org/10.1080/01902148.2022.2052208","url":null,"abstract":"Abstract Objective: This study aims to investigate the protective effect of 3,3′-diindolylmethane (DIM) on the radiation-induced lung injury (RILI) model and to explore its possible mechanism. Methods: A mouse model of RILI was established by thoracic irradiation, and dexamethasone was used as a positive drug to investigate the effect of DIM on RILI mice. Lung histopathology was analyzed by HE staining and Masson staining. Then the levels of inflammatory cytokines (TGF-β, TNF-α, IL-1β, and IL-6), inflammatory cell counts, and activity of MPO were detected. The expression of TGFβ1/Smad signaling pathway-related proteins was determined by immunohistochemistry. qPCR was used to analyze the mRNA expression levels of inflammatory factors, α‑SMA and COL1A1. The expression of COX-2, NF-κB, IκBα, PI3K, and Akt proteins was assessed by Western blot. Results: Histopathological staining of lung tissues showed that DIM administration alleviated the pulmonary inflammation and fibrosis caused by RILI. Moreover, the content of inflammatory factors such as IL-1β and IL-6, the expression of NF-κB pathway-related proteins, and the counts of inflammatory cells were inhibited in lung tissue, indicating that DIM can inhibit the NF-κB pathway to reduce inflammation. In addition, DIM could down-regulate the mRNA levels of α-SMA, COL1A1, and downregulate TGFβ1, Smad3, and p-Smad2/3 in lung tissues. Conclusion: Our study confirms that DIM has the potential to treat RILI in vivo by inhibiting fibrotic and inflammatory responses in lung tissue through the TGFβ/Smad and NF-κB dual pathways, respectively. Graphic Abstract","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"48 1","pages":"103 - 113"},"PeriodicalIF":1.7,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42842496","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":"Correction.","authors":"","doi":"10.1080/01902148.2022.2050526","DOIUrl":"https://doi.org/10.1080/01902148.2022.2050526","url":null,"abstract":"","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":" ","pages":"1-2"},"PeriodicalIF":1.7,"publicationDate":"2022-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905368","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":"Preliminary bronchodilator dose effect on aerosol-delivery through different nebulizers in noninvasively ventilated COPD patients.","authors":"Yasmin M Madney, Hadeer S Harb, Thierry Porée, Myriam Eckes, Marina E Boules, Mohamed E A Abdelrahim","doi":"10.1080/01902148.2022.2047243","DOIUrl":"10.1080/01902148.2022.2047243","url":null,"abstract":"<p><p><b>Objectives:</b> This study aimed to evaluate the effect of a preliminary bronchodilator dose on the aerosol-d elivery by different nebulizers in noninvasively ventilated chronic obstructive pulmonary disease (COPD) patients. <b>Method:</b> COPD patients were randomized to receive study doses of 800 µg beclomethasone dipropionate (BPD) nebulized by either a vibrating mesh nebulizer (VMN) or a jet nebulizer (JN) connected to MinimHal spacer device. On a different day, the nebulized dose of beclomethasone was given to each patient by the same aerosol generator with and without preceded two puffs (100 µg each) of salbutamol delivered by a pressurized-metered dose inhaler. Urinary BPD and its metabolites in 30 min post-inhalation samples and pooled up to 24 h post-inhalation were measured. On day 2, ex-vivo studies were performed with BPD collected on filters before reaching patients which were eluted from filters and analyzed to estimate the total emitted dose.<b>Results:</b> The highest urinary excretion amounts of BPD and its metabolites 30 min and 24 h post-inhalation were identified with pMDI + VMN compared with other regimens(<i>p</i> < 0.001). The amounts of BPD and its metabolites excreted 30 min post inhalation had approximately doubled with pMDI + JN compared with JN delivery (<i>p</i> < 0.05). No significant effect was found in the ex-vivo study results except between VMN and JN with a significant superiority of the VMN (<i>p</i> < 0.001).<b>Conclusion:</b> Using a preliminary bronchodilator dose before drug nebulization significantly increased the effective lung dose of the nebulized drug with both VMNs and JNs. However, adding a preliminary bronchodilator dose increased the 24 hr cumulative urinary amount of the drug representing higher systemic delivery of the drug, which in turn could result in higher systemic side effects.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"48 1","pages":"1-9"},"PeriodicalIF":1.7,"publicationDate":"2022-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42640473","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":"Bronchial epithelial SIRT1 deficiency exacerbates cigarette smoke induced emphysema in mice through the FOXO3/PINK1 pathway.","authors":"Hui Jiang, Yaona Jiang, Yuanri Xu, Dong Yuan, Yaqing Li","doi":"10.1080/01902148.2022.2037169","DOIUrl":"10.1080/01902148.2022.2037169","url":null,"abstract":"<p><p><b>Purpose:</b> Cellular senescence and mitochondrial fragmentation are thought to be crucial components of the cigarette smoke(CS)-induced responses that contribute to the chronic obstructive pulmonary disease (COPD) development as a result of accelerated premature aging of the lung. Although there have been a few reports on the role of sirtuin 1(SIRT1) in mitochondrial homeostasis, senescence and inflammation, whether SIRT1/FOXO3/PINK1 signaling mediated mitophagy ameliorates cellular senescence in COPD is still unclear. This study aimed to ascertain whether SIRT1 regulates cellular senescence via FOXO3/PINK1-mediated mitophagy in COPD. <b>Methods</b>: To investigate the effect of CS exposure and SIRT1 deficiency on mitophagy and senescence in the lung, a SIRT1 knockout(KO) mouse model was used. Airway resistance, cellular senescence mitochondrial injury, mitophagy, cellular architecture and protein expression levels in lung tissues, from SIRT1 KO and wild-type(WT) COPD model mice exposed to CS for 6 months were examined by western blotting, histochemistry, immunofluorescence and transmission electron microscopy(TEM). <b>Results</b>: In CS exposed mice, SIRT1 deficiency exacerbated airway resistance and cellular senescence, increased FOXO3 acetylation and decreased PINK1 protein levels and attenuated mitophagy. Mechanistically, the damaging effect of SIRT1 deficiency on lung tissue was attributed to increased FOXO3 acetylation and decreased PINK1 levels, and attenuated mitophagy. In vitro, mitochondrial damage and cellular sensitivity in response to CS exposure were more severe in control cells than in cells treated with aSIRT1 activator. SIRT1 activation SIRT1 activation decreased FOXO3 acetylation and increased the protein levels of PINK1 and enhanced mitophagy. <b>Conclusion</b>: These results demonstrated that the detrimental effects of SIRT1 deficiency on cell senescence associated with insufficient mitophagy, and involved the FOXO3/PINK1 signaling pathway.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":" ","pages":"1-16"},"PeriodicalIF":1.7,"publicationDate":"2022-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39602570","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":"The 16S rRNA lung microbiome in mechanically ventilated patients: a methodological study.","authors":"Melanie Fromentin,&nbsp;Antoine Bridier-Nahmias,&nbsp;Jérôme Legoff,&nbsp;Severine Mercier-Delarue,&nbsp;Noémie Ranger,&nbsp;Constance Vuillard,&nbsp;Julien Do Vale,&nbsp;Noémie Zucman,&nbsp;Antonio Alberdi,&nbsp;Jean-Damien Ricard,&nbsp;Damien Roux","doi":"10.1080/01902148.2021.2021327","DOIUrl":"https://doi.org/10.1080/01902148.2021.2021327","url":null,"abstract":"<p><strong>Purpose: </strong>Characterization of the respiratory tract bacterial microbiome is in its infancy when compared to the gut microbiota. To limit bias mandates a robust methodology. Specific amplification of the hypervariable (V) region of the 16SrRNA gene is a crucial step. Differences in accuracy exist for one V region to another depending on the sampled environment. We aimed to assess the impact of the primer sequences targeting the V4 region currently used for gut microbiota studies in respiratory samples. <b>Materials and methods</b>: The original 515 F-806R primer pair targets the V4 region of the 16SrRNA gene. We compared two different 515 F-806R primer pairs before Illumina 250 paired-end sequencing for bacterial microbiome analyses of respiratory samples from critically-ill ventilated patients. \"S-V4\" for \"Stringent V4\" primer pair is used in two ongoing international projects \"the Integrative Human microbiome project (iHMP)\" and \"the Earth microbiome project (EMP).\" \"R-V4\" for \"Relaxed V4\" primer pair has been modified to reduce biases against specific environmental taxa. The optimal method was determined by concordance with conventional microbiology. <b>Results</b>: Twenty samples from three patients who developed a ventilator-associated pneumonia (VAP) and four who did not (control ventilated patients) were sequenced. Highly different results were obtained. \"S-V4\" provided the best agreement with the conventional microbiology for endotracheal aspirate: 89% as compared to 56% for \"R-V4.\" The main difference related to poor <i>Enterobacteriaceae</i> detection with \"R-V4\" primers. <b>Conclusions:</b> Accuracy of the bacterial lung microbiome composition was highly dependent on the primers used for amplification of the 16 s rRNA hypervariable sequence. This work validates for future lung microbiome studies the use of the 515 F-806R \"S-V4\" primer pair associated to Illumina® MiSeq paired-end sequencing.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"48 1","pages":"23-34"},"PeriodicalIF":1.7,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39770067","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":"Effects of end-expiratory lung volume versus PaO₂ guided PEEP determination on respiratory mechanics and oxygenation in moderate to severe ARDS.","authors":"Kazim Rollas,&nbsp;Pervin Hanci,&nbsp;Arzu Topeli","doi":"10.1080/01902148.2021.2021326","DOIUrl":"https://doi.org/10.1080/01902148.2021.2021326","url":null,"abstract":"<p><p>There is no ideal method for determination of positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS) patients. We compared the effects of end-expiratory lung volume (EELV)-guided versus PaO₂-guided PEEP determination on respiratory mechanics and oxygenation during the first 48 hours in moderate to severe ARDS.</p><p><p>Twenty-two patients with moderate to severe ARDS admitted to an academic medical ICU were assigned to PaO₂-guided (<i>n</i> = 11) or to EELV-guided PEEP determination (<i>n</i> = 11) group. First, an incremental PEEP trial was performed by increasing PEEP by 3 cmH₂O steps from 8 to 20 cmH₂O and in each step EELV and lung mechanics were measured in both groups. Then, oxygenation and respiratory mechanics were measured under the determined PEEP at 4, 12, 24, and 48th hours.</p><p><p>After the incremental PEEP trial, over the 48 hours of the study period, in the EELV-guided group PaO₂ and PaO₂/FiO₂ increased (<i>p</i> = 0.04 and <i>p</i> = 0.02; respectively), whereas they did not change in PaO₂-guided group (<i>p</i> = 0.09 and <i>p</i> = 0.27; respectively). In all patients, the median value of EELV change (ΔEELV) during incremental PEEP trial was 25%. In patients with ΔEELV > 25% (<i>n</i> = 11) PaO₂, PaO₂/FiO₂ and Cs increased over time in 48 hours (<i>p</i> = 0.03, <i>p</i> < 0.01, and <i>p</i> = 0.04; respectively), whereas they did not change in those with ΔEELV ≤ 25% (<i>n</i> = 11) (<i>p</i> = 0.73, <i>p</i> = 0.51, and <i>p</i> = 0.73; respectively).</p><p><p>Compared to PaO₂-guided PEEP determination, EELV-guided PEEP determination resulted in greater improvement in oxygenation over time. Patients who had > 25% improvement in EELV during a PEEP trial had greater improvement in oxygenation and compliance over 48 hours.</p><p><p>Supplemental data for this article is available online at.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"48 1","pages":"12-22"},"PeriodicalIF":1.7,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39765715","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":"Overexpression of bone morphogenetic protein receptor type 2 suppresses transforming growth factor β-induced profibrotic responses in lung fibroblasts.","authors":"Jun Fukihara,&nbsp;Suzanne Maiolo,&nbsp;Jessica Kovac,&nbsp;Koji Sakamoto,&nbsp;Keiko Wakahara,&nbsp;Naozumi Hashimoto,&nbsp;Paul N Reynolds","doi":"10.1080/01902148.2021.2024301","DOIUrl":"https://doi.org/10.1080/01902148.2021.2024301","url":null,"abstract":"<p><strong>Materials and methods: </strong>We investigated BMPR2 expression in pulmonary fibrosis and TGF-β/BMP signaling in lung fibroblasts. Then we evaluated the impact of BMPR2 upregulation using adenoviral transduction on TGF-β-induced Smad2/3 phosphorylation and fibronectin production in lung fibroblasts.</p><p><strong>Results: </strong>BMPR2 was distributed in airway epithelium and alveolar walls in rat lungs. BMPR2 expression was decreased in fibrotic lesions in the lungs of rats with bleomycin-induced pulmonary fibrosis and in human lung fibroblasts (HLFs) stimulated with TGF-β. Although Smad2/3 phosphorylation and fibronectin production were not suppressed solely by BMPs, phosphorylated Smad2/3 was decreased in BMPR2-transduced cells even without BMP stimulation. Fibronectin was decreased only when BMPR2-transduced HLFs were stimulated with BMP7 (but not BMP4). Similar results were also observed in IPF patient HLFs and rat lung fibroblasts.</p><p><strong>Conclusions: </strong>BMPR2 expression was reduced in fibrotic lungs and lung fibroblasts stimulated with TGF-β. BMPR2 transduction to lung fibroblasts reduced Smad2/3 phosphorylation, and reduced fibronectin production when treated with BMP7. Upregulation of BMPR2 may be a possible strategy for treating pulmonary fibrosis.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"48 1","pages":"35-51"},"PeriodicalIF":1.7,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39916946","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}