American Journal of Respiratory Cell and Molecular Biology最新文献

{"title":"Let-7a-5p Inhibits IL-4-induced MUC5AC Expression and Mucus Hypersecretion and Is Transported in Nasal Lavage Extracellular Vesicles.","authors":"Daeun Jeong, Youn Wook Chung, Haein Ji, Jinsun Kim, Ju Hee Seo, Seunghan Han, Sungmin Moon, Min-Seok Rha, Hyung-Ju Cho, Chang-Hoon Kim, Ji-Hwan Ryu, Hyeon Ho Kim, Joo-Heon Yoon","doi":"10.1165/rcmb.2023-0268LE","DOIUrl":"10.1165/rcmb.2023-0268LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":"71 3","pages":"375-379"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103552","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}

{"title":"The FAM13A Long Isoform Regulates Cilia Movement and Coordination in Airway Mucociliary Transport.","authors":"Ashleigh Howes, Clare Rogerson, Nikolai Belyaev, Tina Karagyozova, Radu Rapiteanu, Ricardo Fradique, Nicola Pellicciotta, David Mayhew, Catherine Hurd, Stefania Crotta, Tanya Singh, Kevin Dingwell, Anniek Myatt, Navot Arad, Hikmatyar Hasan, Hielke Bijlsma, Aliza Panjwani, Vinaya Vijayan, George Young, Angela Bridges, Sebastien Petit-Frere, Joanna Betts, Chris Larminie, James C Smith, Edith M Hessel, David Michalovich, Louise Walport, Pietro Cicuta, Andrew J Powell, Soren Beinke, Andreas Wack","doi":"10.1165/rcmb.2024-0063OC","DOIUrl":"10.1165/rcmb.2024-0063OC","url":null,"abstract":"<p><p>Single nucelotide polymorphisms (SNPs) at the <i>FAM13A</i> locus are among the most commonly reported risk alleles associated with chronic obstructive pulmonary disease (COPD) and other respiratory diseases; however, the physiological role of FAM13A is unclear. In humans, two major protein isoforms are expressed at the <i>FAM13A</i> locus: \"long\" and \"short,\" but their functions remain unknown, partly because of a lack of isoform conservation in mice. We performed in-depth characterization of organotypic primary human airway epithelial cell subsets and show that multiciliated cells predominantly express the FAM13A long isoform containing a putative N-terminal Rho GTPase-activating protein (RhoGAP) domain. Using purified proteins, we directly demonstrate the RhoGAP activity of this domain. In <i>Xenopus laevis</i>, which conserve the long-isoform, Fam13a deficiency impaired cilia-dependent embryo motility. In human primary epithelial cells, long-isoform deficiency did not affect multiciliogenesis but reduced cilia coordination in mucociliary transport assays. This is the first demonstration that FAM13A isoforms are differentially expressed within the airway epithelium, with implications for the assessment and interpretation of SNP effects on <i>FAM13A</i> expression levels. We also show that the long FAM13A isoform coordinates cilia-driven movement, suggesting that <i>FAM13A</i> risk alleles may affect susceptibility to respiratory diseases through deficiencies in mucociliary clearance.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"282-293"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monocytes: See One Queuing Local Adaptive Immune Responses to Respiratory Viruses.","authors":"Alexander P Earhart, Hrishikesh S Kulkarni","doi":"10.1165/rcmb.2024-0195ED","DOIUrl":"10.1165/rcmb.2024-0195ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"259-261"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyrimidine Biosynthesis in Branching Morphogenesis Defects Induced by Prenatal Heavy Metal Exposure.","authors":"Cherry Wongtrakool, Jing Ma, Zachery R Jarrell, Ken H Liu, Michael Orr, ViLinh Tran, Theresa W Gauthier, Carmen J Marsit, Dean P Jones, Young-Mi Go, Xin Hu","doi":"10.1165/rcmb.2024-0123LE","DOIUrl":"10.1165/rcmb.2024-0123LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":"71 3","pages":"372-375"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"September Highlights/Papers by Junior Investigators/NIH News.","authors":"","doi":"10.1165/rcmb.71i3RedAlert","DOIUrl":"https://doi.org/10.1165/rcmb.71i3RedAlert","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":"71 3","pages":"iii-iv"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103554","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}

{"title":"Sodium Houttuyfonate Alleviates Monocrotaline-induced Pulmonary Hypertension by Regulating Orai1 and Orai2.","authors":"Jun Zhang, Fang Dong, Gaojia Ju, Xinli Pan, Xinwu Mao, Xiaowen Zhang","doi":"10.1165/rcmb.2023-0015OC","DOIUrl":"10.1165/rcmb.2023-0015OC","url":null,"abstract":"<p><p>An increased intracellular Ca²⁺ concentration ([Ca²⁺]_i) is a key trigger for pulmonary arterial smooth muscle cell (PASMC) proliferation and contributes greatly to pulmonary hypertension (PH). Extracellular Ca²⁺ influx via a store-operated Ca²⁺ channel, termed store-operated Ca²⁺ entry (SOCE), is a crucial mechanism for [Ca²⁺]_i increase in PASMCs. Calcium release-activated calcium modulator (Orai) proteins, consisting of three members (Orai1-3), are the main components of the store-operated Ca²⁺ channel. Sodium houttuyfonate (SH) is a product of the addition reaction of sodium bisulfite and houttuynin and has antibacterial, antiinflammatory, and other properties. In this study, we assessed the contributions of Orai proteins to monocrotaline (MCT)-enhanced SOCE, [Ca²⁺]_i, and cell proliferation in PASMCs and determined the effect of SH on MCT-PH and the underlying mechanism, focusing on Orai proteins, SOCE, and [Ca²⁺]_i in PASMCs. Our results showed that: <i>1</i>) Orai1 and Orai2 were selectively upregulated in the distal pulmonary arteries and the PASMCs of MCT-PH rats; <i>2</i>) knockdown of Orai1 or Orai2 reduced SOCE, [Ca²⁺]_i, and cell proliferation without affecting their expression in PASMCs in MCT-PH rats; <i>3</i>) SH significantly normalized the characteristic parameters in a dose-dependent manner in the MCT-PH rat model; and <i>4</i>) SH decreased MCT-enhanced SOCE, [Ca²⁺]_i, and PASMC proliferation via Orai1 or Orai2. These results indicate that SH likely exerts its protective role in MCT-PH by inhibiting the Orai1,2-SOCE-[Ca²⁺]_i signaling pathway.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"332-342"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848062","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}

{"title":"Long Story Short: Understanding Isoform-Specific Expression of <i>FAM13A</i>.","authors":"Cera A McDonald, Ryan A Langlois","doi":"10.1165/rcmb.2024-0166ED","DOIUrl":"10.1165/rcmb.2024-0166ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"257-258"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of Sodium Houttuyfonate in Pulmonary Hypertension through Orai-Ca²⁺ Channels.","authors":"Anaïs Saint-Martin Willer, Kristell El Jekmek, Fabrice Antigny","doi":"10.1165/rcmb.2024-0214ED","DOIUrl":"10.1165/rcmb.2024-0214ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"262-263"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung Fibrosis Is Linked to Increased Endothelial Cell Activation and Dysfunctional Vascular Barrier Integrity.","authors":"Elisabeth Fließer, Katharina Jandl, Thomas Lins, Anna Birnhuber, Francesco Valzano, Dagmar Kolb, Vasile Foris, Akos Heinemann, Horst Olschewski, Matthias Evermann, Konrad Hoetzenecker, Michael Kreuter, Norbert F Voelkel, Leigh M Marsh, Malgorzata Wygrecka, Grazyna Kwapiszewska","doi":"10.1165/rcmb.2024-0046OC","DOIUrl":"10.1165/rcmb.2024-0046OC","url":null,"abstract":"<p><p>Pulmonary fibrosis (PF) can be a fatal disease characterized by progressive lung scarring. It is still poorly understood how the pulmonary endothelium is involved in the disease pathogenesis. Differences of the pulmonary vasculature between patients and donors were analyzed using transmission electron microscopy, immunohistochemistry, and single-cell RNA sequencing. Vascular barrier resistance, endothelial-immune cell adhesion, and sensitivity to an inflammatory milieu were studied <i>in vitro</i>. Integrity and activation markers were measured by ELISA in human plasma. Transmission electron microscopy demonstrated abnormally swollen endothelial cells (ECs) in fibrotic lungs compared with donors. A more intense CD31 and von Willebrand Factor (vWF) and patchy vascular endothelial (VE)-Cadherin staining in fibrotic lungs supported the presence of a dysregulated endothelium. Integrity markers CD31, VE-Cadherin, Thrombomodulin, and VEGFR-2 (vascular endothelial growth factor receptor-2) and activation marker vWF gene expression was increased in different endothelial subpopulations (e.g., arterial, venous, general capillary, aerocytes) in PF. This was associated with a heightened sensitivity of fibrotic ECs to TNF-α or IFN-γ and elevated immune cell adhesion. The barrier strength was overall reduced in ECs from fibrotic lungs. vWF and IL-8 were increased in the plasma of patients, whereas VE-Cadherin, Thrombomodulin, and VEGFR-2 were decreased. VE-Cadherin staining was also patchy in biopsy tissue and was decreased in plasma samples of patients with PF 6 months after the initial diagnosis. Our data demonstrate highly abnormal ECs in PF. The vascular compartment is characterized by hyperactivation and increased immune cell adhesion, as well as dysfunctional endothelial barrier function. Reestablishing EC homeostasis and function might represent a new therapeutic option for fibrotic lung diseases.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"318-331"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282724","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}

{"title":"Collagen 18A1/Endostatin Expression in the Progression of Right Ventricular Remodeling and Dysfunction in Pulmonary Arterial Hypertension.","authors":"Anjira S Ambade, Mario Naranjo, Tijana Tuhy, Rose Yu, Mery Marimoutou, Allen D Everett, Larissa A Shimoda, Stefan L Zimmerman, Ilton M Cubero Salazar, Catherine E Simpson, Ryan J Tedford, Steven Hsu, Paul M Hassoun, Rachel L Damico","doi":"10.1165/rcmb.2024-0039OC","DOIUrl":"10.1165/rcmb.2024-0039OC","url":null,"abstract":"<p><p>Numerous studies have demonstrated that endostatin (ES), a potent angiostatic peptide derived from collagen type XVIII α 1 chain and encoded by <i>COL18A1</i>, is elevated in pulmonary arterial hypertension (PAH). It is important to note that elevated ES has consistently been associated with altered hemodynamics, poor functional status, and adverse outcomes in adult and pediatric PAH. This study used serum samples from patients with Group I PAH and plasma and tissue samples derived from the Sugen/hypoxia rat pulmonary hypertension model to define associations between <i>COL18A1</i>/ES and disease development, including hemodynamics, right ventricle (RV) remodeling, and RV dysfunction. Using cardiac magnetic resonance imaging and advanced hemodynamic assessments with pressure-volume loops in patients with PAH to assess RV-pulmonary arterial coupling, we observed a strong relationship between circulating ES levels and metrics of RV structure and function. Specifically, RV mass and the ventricular mass index were positively associated with ES, whereas RV ejection fraction and RV-pulmonary arterial coupling were inversely associated with ES levels. Our animal data demonstrate that the development of pulmonary hypertension is associated with increased <i>COL18A1</i>/ES in the heart as well as the lungs. Disease-associated increases in <i>COL18A1</i> mRNA and protein were most pronounced in the RV compared with the left ventricle and lung. <i>COL18A1</i> expression in the RV was strongly associated with disease-associated changes in RV mass, fibrosis, and myocardial capillary density. These findings indicate that <i>COL18A1</i>/ES increases early in disease development in the RV and implicates <i>COL18A1</i>/ES in pathologic RV dysfunction in PAH.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"343-355"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11376241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}