Experimental Lung Research最新文献

{"title":"Effect of using acoustic flo-tone training device and its smartphone application on enhancing inhalation technique from metered-dose inhaler with spacer in asthmatic children.","authors":"Sara M Tony,&nbsp;Mona A Abdelrahman,&nbsp;Mogeda Abd Elsalam,&nbsp;Mahmoud Sameer Shafik,&nbsp;Mohamed E A Abdelrahim","doi":"10.1080/01902148.2022.2113573","DOIUrl":"https://doi.org/10.1080/01902148.2022.2113573","url":null,"abstract":"<p><p><b>Aim of study:</b> This research study aims to compare between two different counseling approaches; traditional verbal counseling vs. advanced counseling (in which we used the acoustic Flo-tone training device and its smartphone application combined with traditional verbal counseling) to determine the most beneficial counseling approach for asthmatic children who use metered-dose inhaler (MDI) with spacers concerning inhalation duration and inhalation technique mistakes. <b>Methods:</b> A total of 100 asthmatic children (8-18) years old were randomized into two groups (a control group, and an advanced group). Each group included 50 subjects. Every subject received 3 counseling meetings, one each month. Asthmatic children in the control group were trained on inhalation technique from MDI + spacer verbally (traditional counseling), while asthmatic children in advanced group were trained on inhalation technique from MDI + spacer verbally and by advanced counseling (whistling Flo-tone + smartphone application). At each visit mistakes in inhalation technique steps were; detected, corrected, and recorded and the inhalation duration was measured for every child in each group. <b>Results:</b> In both study groups, the total mean number of inhalation technique mistakes decreased significantly (p < 0.05) from visit 2, also the total mean inhalation durations in seconds showed a significant increase (p < 0.05) from visit 2. A significant (p < 0.05) reduction in the total mean number of mistakes and a significant (p < 0.05) increase in total mean inhalation durations were observed from visit 2 in advanced group compared to control group. <b>Conclusion:</b> Combination between traditional verbal and advanced counseling methods resulted in significant (P < 0.05) improvements in the number of inhalation technique mistakes and inhalation durations from MDI with spacer in children compared to using traditional verbal counseling alone.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"48 7-8","pages":"224-238"},"PeriodicalIF":1.7,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40649108","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":"BRD7 restrains TNF-α-induced proliferation and migration of airway smooth muscle cells by inhibiting notch signaling.","authors":"Hong Li,&nbsp;Tian Yang,&nbsp;Tianjun Chen,&nbsp;Ya Liu,&nbsp;Yamei Pang,&nbsp;Lan Yang","doi":"10.1080/01902148.2022.2107730","DOIUrl":"https://doi.org/10.1080/01902148.2022.2107730","url":null,"abstract":"<p><p><b>Objective</b>: Bromodomain-containing protein 7 (BRD7) is a key component of the switch/sucrose non-fermentable complex that participates in chromatin remodeling and transcriptional regulation. Although the emerging role of BRD7 in the pathophysiology of various diseases has been observed, its role in asthma remains unknown. Here, we assessed the function of BRD7 as a mediator of airway remodeling in asthma using an <i>in vitro</i> model. <b>Methods:</b> Airway smooth muscle cells (ASMCs) were challenged with tumor necrosis factor-α (TNF-α) to establish an <i>in vitro</i> airway remodeling model. Protein levels were examined using western blotting. Cell proliferation was measured using the cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays. Cell migration was assessed using a transwell migration assay. <b>Results:</b> Exposure to TNF-α dramatically decreased BRD7 levels in ASMCs. BRD7 remarkably decreased TNF-α-induced proliferation and migration of ASMCs. In contrast, ASMCs with BRD7 deficiency were more sensitive to TNF-α-induced pro-proliferative and pro-migratory effects. Mechanistically, BRD7 could repress the expression of Notch1 and block the Notch pathway in TNF-α-challenged cells. Notably, reactivation of Notch signaling substantially reversed the BRD7 overexpression-mediated effects, whereas restraining Notch signaling abolished BRD7-depletion-mediated effects on TNF-α-challenged cells. <b>Conclusions:</b> BRD7 inhibits the proliferation and migration of ASMCs elicited by TNF-α by downregulating the Notch pathway. This study indicates that BRD7 may exert a suppressive effect on airway remodeling during asthma.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"48 7-8","pages":"199-212"},"PeriodicalIF":1.7,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40692631","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>Lef1</i> is transcriptionally activated by <i>Klf4</i> and suppresses hyperoxia-induced alveolar epithelial cell injury.","authors":"Min Yang,&nbsp;Xueshan Huang,&nbsp;Fang Shen,&nbsp;Juanjuan Yi,&nbsp;Yanni Meng,&nbsp;Yanping Chen","doi":"10.1080/01902148.2022.2108945","DOIUrl":"https://doi.org/10.1080/01902148.2022.2108945","url":null,"abstract":"<p><strong>Purpose: </strong>Bronchopulmonary dysplasia (BPD) is a long-term respiratory condition. More than a quarter of extremely premature newborns are harmed by BPD. At present, there are no apparent effective drugs or treatments for the condition. In this study, we aimed to investigate the functional role and mechanism of lymphoid enhancer-binding factor 1 (<i>Lef1</i>) in BPD <i>in vitro</i>.</p><p><strong>Materials and methods: </strong>Blood samples from BPD patients and healthy volunteers were gathered, and an <i>in vitro</i> model of BPD was developed in alveolar epithelial cells (AECs) MLE-12 induced by hyperoxia. Then expression of krüppel-like factor 4 (<i>KLF4</i>/<i>Klf4</i>) and <i>LEF1</i>/<i>Lef1</i> were evaluated. After <i>Lef1</i> overexpressing plasmid and the vector were transfected into hyperoxia-induced MLE-12 cells, cell proliferation assays were carried out. Cell apoptosis was investigated by a flow cytometry assay, and apoptosis related proteins Bcl-2, cleaved-caspase 3 and 9 were analyzed by a western blot assay. The binding between <i>Klf4</i> and <i>Lef1</i> promoter predicted on the JASPAR website was verified using luciferase and ChIP assays. For further study of the mechanism of <i>Klf4</i> and <i>Lef1</i> in BPD, gain-of-function experiments were performed.</p><p><strong>Results: </strong>The mRNA levels of <i>KLF4</i>/<i>Klf4</i> and <i>LEF1</i>/<i>Lef1</i> were diminished in clinical BPD serum samples and hyperoxia-induced MLE-12 cells. Overexpression of <i>Lef1</i> stimulated AEC proliferation and suppressed AEC apoptosis induced by hyperoxia. Mechanically, <i>Klf4</i> bound to <i>Lef1</i>'s promoter region and aids transcription. Moreover, the results of gain-of-function experiments supported that <i>Klf4</i> could impede AEC damage induced by hyperoxia via stimulating <i>Lef1</i>.</p><p><strong>Conclusion: </strong><i>Klf4</i> and <i>Lef1</i> expression levels were declined in hyperoxia-induced AECs, and <i>Lef1</i> could be transcriptionally activated by <i>Klf4</i> and protect against hyperoxia-induced AEC injury in BPD. As a result, <i>Lef1</i> might become a prospective therapeutic target for BPD.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"48 7-8","pages":"213-223"},"PeriodicalIF":1.7,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40685138","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":"Aerosol inhalation of <i>Mycobacterium vaccae</i> ameliorates airway structural remodeling in chronic asthma mouse model.","authors":"Qian-Nan Zhang,&nbsp;Huan Xiao,&nbsp;Li-Ting Fang,&nbsp;Qi-Xiang Sun,&nbsp;Lao-Dong Li,&nbsp;Si-Yue Xu,&nbsp;Chao-Qian Li","doi":"10.1080/01902148.2022.2115166","DOIUrl":"https://doi.org/10.1080/01902148.2022.2115166","url":null,"abstract":"<p><p><b>Background:</b> Airway remodeling is accepted to be a determining component within the natural history of asthma. Nebulized inhalation of <i>Mycobacterium vaccae</i> (<i>M. vaccae</i>) has a protective effect on asthmatic mice. However, little is known regarding the effect of <i>M. vaccae</i> on airway structural remodeling in asthmatic mice. The purpose of this study was to explore the effect and the underlying mechanism of <i>M. vaccae</i> aerosol inhalation on airway structural remodeling in an asthma mouse model. <b>Methods:</b> Chronic asthma mouse models were established by ovalbumin induction. The number of inflammatory cells in bronchoalveolar lavage fluid (BALF), pathological alterations in lung tissue, and levels of associated cytokines (IL-5, IL-13, TNF-α, and ovalbumin-specific immunoglobulin E [OVA-sIgE]) were all assessed after <i>M. vaccae</i> therapy. The relative expression of interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), and Wnt1-induced signaling protein 1 (WISP1) mRNA were detected. Western blotting and immunohistochemistry detected the expression of Wnt/β-catenin pathway-related proteins in lung tissue. <b>Results:</b> <i>M. vaccae</i> aerosol inhalation relieved airway inflammation, airway hyper-responsiveness, and airway remodeling. <i>M. vaccae</i> reduced the levels of IL-5, IL-13, TNF-α, and OVA-sIgE in and downregulated the expression of IL-1β, TNF-α, NF-κB, and WISP1 mRNA in the pulmonary. In addition, <i>M. vaccae</i> inhibited the expression of β-catenin, WISP1, and Wnt1 protein and upregulated the expression of glycogen synthase kinase-3beta (GSK-3β). <b>Conclusion:</b> Nebulized inhalation of <i>M. vaccae</i> can reduce airway remodeling during asthma.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"48 7-8","pages":"239-250"},"PeriodicalIF":1.7,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40412180","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":"Metabolic profile of exhaled breath condensate from the pneumonia patients","authors":"Xiaoguang Li, J. Du, Jing Chen, F. Lin, Wei Wang, Tingqiu Wei, Jie Xu, Q. Lu","doi":"10.1080/01902148.2022.2078019","DOIUrl":"https://doi.org/10.1080/01902148.2022.2078019","url":null,"abstract":"Abstract Purpose of the Study Exhaled breath condensate (EBC) is increasingly being used for disease diagnosis and environmental exposure assessment as a noninvasive method reducing the risk of exposure. The purpose of this study was to investigate the application of a new sample type of EBC in pneumonia by metabolomics and to explore differential metabolites and potential metabolic pathways. Materials and Methods A case-control study was performed at the Peking University Third Hospital from August to December 2020. C-MS/MS analyses were performed on EBC samples using a UHPLC system. Results Totally 22 patients with pneumonia and 24 healthy controls were recruited. Using untargeted metabolomics based on LC-MS/MS analysis, 25 kinds of differential metabolites were found. Through a comprehensive analysis of the pathways in which the differential metabolites were located, the key pathway with the highest correlation with the difference of metabolites was taurine and hypotaurine metabolism. Conclusions The study implicates that the hypotaurine/taurine metabolic pathway may play a role on the development of pneumonia through metabolism analysis on EBC and the 3-Sulfinoalanine may be used as a biomarker in the diagnosis of pneumonia.","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"48 1","pages":"149 - 157"},"PeriodicalIF":1.7,"publicationDate":"2022-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44151044","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":"TGF-β-induced CCR8 promoted macrophage transdifferentiation into myofibroblast-like cells.","authors":"Haijun Liu, Qingzhou Guan, Peng Zhao, Jiansheng Li","doi":"10.1080/01902148.2022.2055227","DOIUrl":"10.1080/01902148.2022.2055227","url":null,"abstract":"<p><p><b>Background:</b> Idiopathic pulmonary fibrosis (IPF) is an interstitial disease of unknown origin, characterized by tissue fibrosis, for which currently there is no effective treatment. Macrophages, the main immune cells in lung tissue, are involved in the whole process of pulmonary fibrosis. In recent years, intercellular transformation has led to wide spread concern among pulmonary fibrosis researchers. Macrophages with flexible heterogeneity and plasticity participate in different physiological processes in the body. Cell chemokine receptor 8 (CCR8) is expressed in a variety of cells and plays a significant chemotactic role in the induction of cell activation and migration. It can also promote the differentiation of macrophages under certain environmental conditions. The current study is intended to explore the role of CCR8 in macrophage to myofibroblast transdifferentiation (MMT) in IPF. <b>Methods:</b> We conducted experiments using CCR8-specific small interfering RNA (siRNA), an autophagy inhibitor (3-methyladenine, 3-MA), and an agonist (rapamycin) to explore the underlying mechanisms of macrophage transdifferentiation into myofibroblast cells in transforming growth factor-beta (TGF-β)-induced pulmonary fibrosis. <b>Results:</b> TGF-β treatment increased the CCR8 protein level in a time- and dose-dependent manner in mouse alveolar macrophages, as well as macrophage transdifferentiation-related markers, including vimentin, collagen 1, and a-SMA, and cell migration. In addition, the levels of autophagy were enhanced in macrophages treated with TGF-β. We found that 3-MA, an autophagy inhibitor, decreased the expression levels of macrophage transdifferentiation-related markers and attenuated cell migration. Furthermore, the inhibition of CCR8 via <i>CCR8</i>-specific siRNA reduced the levels of autophagy and macrophage transdifferentiation-related markers, and inhibited the cell migration. Enhancing autophagy with rapamycin attenuated the inhibition effect of <i>CCR8</i>-specific siRNA on macrophage migration and the increase in myofibroblast marker proteins. <b>Conclusions:</b> Our findings showed that the macrophages exposed to TGF-β had the potential to transdifferentiate into myofibroblasts and CCR8 was involved in the process. The effect of CCR8 on TGF-β-induced macrophage transdifferentiation occurs mainly through autophagy. Targeting CCR8 may be a novel therapeutic strategy for the treatment of IPF.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"48 1","pages":"1-14"},"PeriodicalIF":1.7,"publicationDate":"2022-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42416628","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":"SRC3 deficiency exacerbates lipopolysaccharide-induced acute respiratory distress syndrome in mice.","authors":"Meixia Cui,&nbsp;Shengtong Guo,&nbsp;Ying Cui","doi":"10.1080/01902148.2022.2104958","DOIUrl":"https://doi.org/10.1080/01902148.2022.2104958","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) is a severe disease. Inflammation is the key element implicated in ARDS. Steroid receptor coactivator 3 (SRC3), a coactivator protein for transcription, is involved in regulation of inflammatory response. Here we explored the potential roles of SRC3 in ARDS. We utilized the SRC3 deficient (SRC3^-/-) mice and established the lipopolysaccharides (LPS)-induced ARDS model. The mortality, lung injury, leucocytes infiltration and inflammatory cytokine production were compared between wild type (WT) and SRC3^-/- mice. The NF-κB activation in lung of WT and SRC3^-/- mice was measured. After LPS treatment, SRC3^-/- mice had higher mortality and more severe lung damage than WT mice. LPS-treated SRC3^-/- mice had more leucocytes infiltration and upregulated inflammatory cytokine production. LPS-treated SRC3^-/- mice had elevated NF-κB activation. SRC3^-/- mice had exacerbated ARDS in LPS-treated mice.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":" ","pages":"178-186"},"PeriodicalIF":1.7,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40663696","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":"Pulmonary inflammation caused by cigarette smoke combined with lipopolysaccharide up-regulated OATP2B1 in rat lung tissue and pulmonary epithelial cells.","authors":"Zihao Wang, Xin Fang, Shuyi Zhang, Jue Song","doi":"10.1080/01902148.2022.2066223","DOIUrl":"10.1080/01902148.2022.2066223","url":null,"abstract":"<p><p>Organic anion transport polypeptide 2B1 (OATP2B1), as an uptake transporter, is involved in the transport of many related substrate drugs and endogenous substances in the lungs. A large amount of data shows that cigarette smoke plays an important role in the occurrence and development of lung diseases such as chronic obstructive pulmonary disease (COPD), asthma and bronchitis. However, the effect of cigarette smoke combined with lipopolysaccharide-induced pulmonary inflammation on the expression of OATP2B1 is not clear. In this study, we used cigarette smoke combined with lipopolysaccharide to establish a lung inflammation model in vivo and in vitro to explore the effect of inflammation on the expression of OATP2B1. Our study found that cigarette smoke combined with lipopolysaccharide-induced pulmonary inflammation upregulated the mRNA and protein expression of OATP2B1 and related inflammatory factors, and the expression level of related proteins was higher with the aggravation of inflammation. The experimental results of animals in vivo were consistent with those of cells in vitro. In summary, these findings provide a model and basis for a follow-up study of the mechanism of OATP2B1 in pulmonary inflammation.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":"48 1","pages":"114-125"},"PeriodicalIF":1.7,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44766005","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":"Low tidal volume ventilation alleviates ventilator-induced lung injury by regulating the NLRP3 inflammasome.","authors":"Lixia Wang,&nbsp;Jun Li,&nbsp;Yan Zhu,&nbsp;Binshan Zha","doi":"10.1080/01902148.2022.2104409","DOIUrl":"https://doi.org/10.1080/01902148.2022.2104409","url":null,"abstract":"<p><strong>Purpose: </strong>Low tidal volume ventilation (LTVV) is a well-known ventilation mode which can improve ventilator-induced lung injury (VILI). However, the mechanism of LTVV ameliorating VILI has not yet been elucidated. In this study, we aimed to reveal LTVV protected against VILI by inhibiting the activation of the NLRP3 inflammasome in bronchoalveolar lavage fluid (BALF) from humans and lungs from mice.</p><p><strong>Materials and methods: </strong>Twenty-eight patients scheduled for video-assisted thoracoscopic esophagectomy were randomized to receive high-tidal-volume ventilation [<i>V_t</i> = 10 mL/kg without positive end-expiratory pressure (PEEP)] or LTVV (<i>V_t</i> = 5 mL/kg along with 5 cm of H₂O PEEP) during one-lung ventilation. BALF was collected before and at the end of surgery. Male C57BL/6 mice received high-tidal-volume ventilation, LTVV or MCC950 (an inhibitor of NLRP3). The activation of the formation of NLRP3 inflammasome in BALF from patients and in lungs from mice were analyzed.</p><p><strong>Results: </strong>LTTV decreased the peak airway pressure (<i>P</i>_peak), plateau airway pressure (<i>P</i>_plat) and driving pressure (Δ<i>P</i>) during one-lung ventilation. Additionally, LTVV not only inhibited pulmonary infiltration and inflammation caused by mechanical ventilation, but also suppressed the NLRP3 inflammasome activation in BALF from humans. In mice, ventilator-induced inflammatory response and pulmonary edema were suppressed by LTVV with an efficacy comparable to that of MCC950 treatment. Furthermore, LTVV, similar to MCC950, clearly decreased ventilator-induced NLRP3 inflammasome activation.</p><p><strong>Conclusion: </strong>Our study showed that LTVV played a protective role in ventilator-induced lung injury by suppressing the activation of the NLRP3 inflammasome.</p><p><strong>Trial registration: </strong>This study was registered in The Chinese Clinical Trial Registry, ChiCTR1900026190 on 25 September 2019.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":" ","pages":"168-177"},"PeriodicalIF":1.7,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40594060","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":"Downregulation of miR-761 ameliorates radiation-induced pulmonary fibrosis by regulating PGC-1α.","authors":"Zeng Wang,&nbsp;Junying Chen,&nbsp;Li Su,&nbsp;Jinsheng Hong","doi":"10.1080/01902148.2022.2104407","DOIUrl":"https://doi.org/10.1080/01902148.2022.2104407","url":null,"abstract":"<p><p><b>Background:</b> Radiation-induced pulmonary fibrosis (RIPF) is a serious complication in patients treated with transthoracic irradiation. To date, there are no effective drugs for RIPF treatment. In this study, we attempted to explore the function of miR-761 in RIPF, further investigate its potential mechanism and evaluate its effectiveness in the treatment of RIPF. <b>Methods:</b> qRT-PCR analysis was used to detect miR-761 and peroxisome proliferator-activated receptor gamma (PPARg) coactivator-1 (PGC-1α) expression. Western Blot (WB) assay was applied to verify the regulation of PGC-1α by miR-761 and the expression of fibrosis-related proteins. Gel contraction assay was performed to demonstrate the level of fibroblast activation in vitro. A mouse RIPF model was used to validate the anti-fibrotic effect of Antagomir761. Bioinformatics analysis and dual-luciferase reporter assays were utilized to confirm the regulation relationship between miR-761 and PGC-1α. <b>Results:</b> The results showed that miR-761 was significantly elevated in irradiated mice lungs and fibroblasts. Overexpression of miR-761 in vitro promoted fibroblast activation. Whereas inhibition of miR-761 attenuated the degree of RIPF and inhibited fibroblast activation. Mechanistically, PGC-1α was a direct and functional target of miR-761, overexpression of PGC-1α inhibited irradiation-induced fibroblast activation, and knockdown of PGC-1α caused miR-761 inhibitor loses its anti-activation ability in irradiated cells. <b>Conclusion:</b> Our findings demonstrated that miR-761 regulated RIPF by targeting PGC-1α. Inhibition of miR-761 restored PGC-1α expression and attenuated RIPF damage, and miR-761 was a potential target for preventing the development of RIPF.</p>","PeriodicalId":12206,"journal":{"name":"Experimental Lung Research","volume":" ","pages":"158-167"},"PeriodicalIF":1.7,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40572243","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}