American Journal of Respiratory Cell and Molecular Biology最新文献_第4页

Balancing Act: PD-1, PD-L1, and the Inflammatory Tightrope of Acute Respiratory Distress Syndrome. 平衡法：PD-1、PD-L1 和 ARDS 的炎症紧箍咒。

IF 8.3 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-11-01 DOI: 10.1165/rcmb.2024-0339ED

Kara J Mould, William J Janssen

引用次数: 0

Human Lung Cell Separation Strategies for Translational Research. 转化研究中的人类肺细胞分离策略。

IF 8.3 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-11-01 DOI: 10.1165/rcmb.2024-0338LE

Naoya Fujino, Mitsuhiro Yamada, Takuya Saito, Shuichi Konno, Hisatoshi Sugiura

引用次数: 0

VRAC Complex Modulates Mechano-Electrical Signal Responses in Human Airway Smooth Muscle Shortening. VRAC 复合物调节人气道平滑肌缩短过程中的机电信号反应

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-10-29 DOI: 10.1165/rcmb.2024-0160OC

Joanna Woo, Gaoyuan Cao, Nikhil Karmacharya, Jordan Lee, Justin Lee, Kingsley C Duru, Conor McClenaghan, Steven S An, Reynold A Panettieri, Joseph A Jude

{"title":"VRAC Complex Modulates Mechano-Electrical Signal Responses in Human Airway Smooth Muscle Shortening.","authors":"Joanna Woo, Gaoyuan Cao, Nikhil Karmacharya, Jordan Lee, Justin Lee, Kingsley C Duru, Conor McClenaghan, Steven S An, Reynold A Panettieri, Joseph A Jude","doi":"10.1165/rcmb.2024-0160OC","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0160OC","url":null,"abstract":"Leucine-rich repeat containing 8A (LRRC8A) is an obligatory constituent of the volume-regulated anion channel (VRAC) that is fundamental to a wide range of biological processes, including regulating cell size, proliferation, and migration. Here we explored the physiological role for VRAC in excitation-contraction (E-C) coupling and shortening of human airway smooth muscle (HASM). In HASM cells, pharmacological inhibition of VRAC with DCPIB (0.1-10 μM) markedly attenuated swell-activated Cl- conductance and contractile agonist (histamine or carbachol)-induced cellular stiffening as measured by single-cell patch clamp and optical magnetic twisting cytometry, respectively. In addition, HASM cells treated with DCPIB or transfected with LRRC8A-targeting siRNA showed reduced agonist-induced phosphorylation of protein kinase B (AKT), paxillin, myosin phosphatase target subunit 1 (MYPT1), and myosin light chain (MLC). Consistent with the changes of these E-C coupling effectors, DCPIB appreciably decreased agonist-induced small airways narrowing in human precision-cut lung slices (hPCLS). Taken together, our findings shed a new light on the mechanistic link between HASM shortening and regulatory volume decrease via LRRC8A, revealing a previously unrecognized nodal point for modulation of the E-C coupling and acute airways constriction.","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Guarding the Endothelium: SOX17's Crucial Role in Pulmonary Hypertension. 守护内皮：SOX17在肺动脉高压中的关键作用

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-10-29 DOI: 10.1165/rcmb.2024-0490ED

Xinyi Zhang, Zhiyu Dai

引用次数: 0

Cracking the Code of the Jugular Vagal Sensory Neurons in Allergic Airway Responsiveness. 破解过敏性气道反应中颈静脉感觉神经元的密码

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-10-29 DOI: 10.1165/rcmb.2024-0445ED

Aung Aung Kywe Moe

引用次数: 0

FSP1 Acts in Parallel with GPX4 to Inhibit Ferroptosis in COPD. FSP1 与 GPX4 并行抑制慢性阻塞性肺病中的铁氧化作用

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-10-25 DOI: 10.1165/rcmb.2023-0467OC

Yue Yang, Weiyu Shen, Zheming Zhang, Youai Dai, Zixiao Zhang, Tingting Liu, Jinyan Yu, Shulun Huang, Yu Ding, Rong You, Ziteng Wang, Yan Wu, Tao Bian

{"title":"FSP1 Acts in Parallel with GPX4 to Inhibit Ferroptosis in COPD.","authors":"Yue Yang, Weiyu Shen, Zheming Zhang, Youai Dai, Zixiao Zhang, Tingting Liu, Jinyan Yu, Shulun Huang, Yu Ding, Rong You, Ziteng Wang, Yan Wu, Tao Bian","doi":"10.1165/rcmb.2023-0467OC","DOIUrl":"10.1165/rcmb.2023-0467OC","url":null,"abstract":"Glutathione peroxidase 4 (GPX4) has recently been reported to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Ferroptosis suppressor protein-1 (FSP1) is a protein that defends against ferroptosis in parallel with GPX4, but its role in the pathogenesis of COPD remains unexplored, and further research is needed. Normal and COPD lung tissues were obtained from lobectomy and lung transplant specimens, respectively. FSP1-overexpressing mice were established by monthly transfection with AAV9-FSP1 through modified intranasal administration. The expression of FSP1, GPX4, and prostaglandin-endoperoxide synthase 2 (PTGS2) was measured by Western blotting, immunohistochemistry and other methods. The correlation between FSP1 and ferroptosis and the role of FSP1 in COPD were explored by screening the expression of ferroptosis-related genes in a COPD cell model after the inhibition and overexpression of FSP1. We then explored the underlying mechanism of low FSP1 expression in patients with COPD in vitro by methylated RNA immunoprecipitation (MeRIP)-qPCR. We found that cigarette smoke exposure can lead to an increase in lipid peroxide production and ultimately ferroptosis, which is negatively regulated by FSP1 activity. FSP1 overexpression can prevent ferroptosis and alleviate emphysema. Next, we found that decreased FSP1 expression was caused by increased m6A modification of FSP1 mRNA. Moreover, the level of FSP1 decreased in a YTHDF2-dependent manner. These results indicate that METTL3-induced FSP1 mRNA methylation leading to low FSP1 expression is a potential therapeutic target for COPD. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chronic Hypoxia in an EXTrauterine Environment for Neonatal Development Impairs Lung Development. 宫外环境中的慢性缺氧会影响新生儿肺部发育

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-10-25 DOI: 10.1165/rcmb.2024-0012OC

Maureen Peers de Nieuwburgh, Mallory Hunt, Prashant Chandrasekaran, Tiffaney L Vincent, Kevin B Hayes, Isabel R Randazzo, Meredith Gunder, Felix R De Bie, Arthur Colson, Minqi Lu, Hongbo Wen, Sylvia N Michki, Jack Rychik, Fréderic Debiève, Jeremy Katzen, Lisa R Young, Marcus G Davey, Alan W Flake, J William Gaynor, David B Frank

{"title":"Chronic Hypoxia in an EXTrauterine Environment for Neonatal Development Impairs Lung Development.","authors":"Maureen Peers de Nieuwburgh, Mallory Hunt, Prashant Chandrasekaran, Tiffaney L Vincent, Kevin B Hayes, Isabel R Randazzo, Meredith Gunder, Felix R De Bie, Arthur Colson, Minqi Lu, Hongbo Wen, Sylvia N Michki, Jack Rychik, Fréderic Debiève, Jeremy Katzen, Lisa R Young, Marcus G Davey, Alan W Flake, J William Gaynor, David B Frank","doi":"10.1165/rcmb.2024-0012OC","DOIUrl":"10.1165/rcmb.2024-0012OC","url":null,"abstract":"Severe fetal hypoxia poses a significant risk to lung development resulting in severe postnatal complications. Existing chronic hypoxia animal models lack the ability to achieve pathologically reduced fetal oxygen without compromising animal development, placental blood flow, or maternal health. Using an established model of isolated chronic hypoxia involving the Extrauterine Environment for Neonatal Development (EXTEND), we are able to investigate the direct impact of fetal hypoxia on lung development. Oxygen delivery to preterm fetal lambs (105-110 days GA) delivered by cesarean section was reduced, and animals were supported on EXTEND through the canalicular or saccular stage of lung development. Fetal lambs in hypoxic conditions showed significant growth restriction compared to their normoxic counterparts. We also observed modest aberrant vascular remodeling in the saccular group after hypoxic conditions with decreased macrovessel numbers, microvascular endothelial cell numbers, and increased peripheral vessel muscularization. In addition, fetal hypoxia resulted in enlarged distal airspaces and decreased septal wall volume. Moreover, there was a reduction in mature SFTPB and processed SFTPC protein expression concomitant with a decrease in AT2 cell number. These findings demonstrate that maternally-independent fetal hypoxia predominantly impacts distal airway development, AT2 cell number, and surfactant production with mild effects on the vasculature.","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Requirement for Fucosyltransferase 2 in Allergic Airway Hyperreactivity and Mucus Obstruction. 过敏性气道高反应性和粘液阻塞对岩藻糖基转移酶 2 的要求

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-10-24 DOI: 10.1165/rcmb.2024-0216OC

Naoko Hara, Dorota S Raclawska, Leslie E Morgan, James C NeeDell, Lucie Dao, Ayako Kato, Ana M Jaramillo, Patrick S Hume, Fernando Holguin, William J Janssen, Eszter K Vladar, Christopher M Evans

{"title":"Requirement for Fucosyltransferase 2 in Allergic Airway Hyperreactivity and Mucus Obstruction.","authors":"Naoko Hara, Dorota S Raclawska, Leslie E Morgan, James C NeeDell, Lucie Dao, Ayako Kato, Ana M Jaramillo, Patrick S Hume, Fernando Holguin, William J Janssen, Eszter K Vladar, Christopher M Evans","doi":"10.1165/rcmb.2024-0216OC","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0216OC","url":null,"abstract":"Mucus hypersecretion is an important pathological problem in respiratory diseases. Mucus accumulates in the airways of people with asthma, and it contributes to airflow limitation by forming plugs that occlude airways. Current treatments have minimal effects on mucus or its chief components, the polymeric mucin glycoproteins MUC5AC and MUC5B. This treatment gap reflects a poor molecular understanding of mucins that could be used to determine how they contribute to airway obstruction. Due to the prominence of glycosylation as a defining characteristic of mucins, we investigated characteristics of mucin glycans in asthma and in a mouse model of allergic asthma. Mucin fucosylation was observed in asthma, and in healthy mice it was induced as part of a mucous metaplastic response to allergic inflammation. In allergically inflamed mouse airways, mucin fucosylation was dependent on the enzyme fucosyltransferase 2 (Fut2). Fut2 gene deficient mice were protected from asthma-like airway hyperreactivity and mucus plugging. These findings provide mechanistic and translational links between observations in human asthma and a mouse model that may help improve therapeutic targeting of airway mucus.","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

No Pain, No Gain (and No Cough)?: Discrete Brainstem Nuclei Coordinate Reflexive Cough and Pain Responses. 没有痛苦就没有收获（也没有咳嗽）？离散脑干核协调反射性咳嗽和疼痛反应

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-10-24 DOI: 10.1165/rcmb.2024-0432ED

Ubaldo De La Torre, Matthew G Drake

引用次数: 0

Cell Population-resolved Multi-Omics Atlas of the Developing Lung. 发育中肺部的细胞群体分辨多图像图谱

IF 5.9 2区医学

American Journal of Respiratory Cell and Molecular Biology Pub Date : 2024-10-24 DOI: 10.1165/rcmb.2024-0105OC

Mereena G Ushakumary, Song Feng, Gautam Bandyopadhyay, Heather Olson, Karl K Weitz, Heidi L Huyck, Cory Poole, Jeffrey M Purkerson, Soumyaroop Bhattacharya, M Cecilia Ljungberg, Thomas J Mariani, Gail H Deutsch, Ravi S Misra, James P Carson, Joshua N Adkins, Gloria S Pryhuber, Geremy Clair

{"title":"Cell Population-resolved Multi-Omics Atlas of the Developing Lung.","authors":"Mereena G Ushakumary, Song Feng, Gautam Bandyopadhyay, Heather Olson, Karl K Weitz, Heidi L Huyck, Cory Poole, Jeffrey M Purkerson, Soumyaroop Bhattacharya, M Cecilia Ljungberg, Thomas J Mariani, Gail H Deutsch, Ravi S Misra, James P Carson, Joshua N Adkins, Gloria S Pryhuber, Geremy Clair","doi":"10.1165/rcmb.2024-0105OC","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0105OC","url":null,"abstract":"The lung is a vital organ that undergoes extensive morphological and functional changes during postnatal development. To disambiguate how different cell populations contribute to organ development, we performed proteomic and transcriptomic analyses of four sorted cell populations from the lung of human subjects aged 0 to 8 years-old with a focus on early life. The cell populations analyzed included epithelial, endothelial, mesenchymal, and immune cells. Our results revealed distinct molecular signatures for each of the sorted cell populations that enable the description of molecular shifts occurring in these populations during post-natal development. We confirmed that the proteome of the different cell populations was distinct regardless of age and identified functions specific to each population. We identified a series of cell population protein markers, including those located at the cell surface, that show differential expression and distribution on RNA in situ hybridization and immunofluorescence imaging. We validated the spatial distribution of AT1 and endothelial cell surface markers. Temporal analyses of the proteomes of the four populations revealed processes modulated during postnatal development and clarified the findings obtained from whole tissue proteome studies. Finally, the proteome was compared to a transcriptomics survey performed on the same lung samples to evaluate processes under post-transcriptional control.","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0