American Journal of Respiratory Cell and Molecular Biology最新文献

{"title":"The Potential of Extracellular Microvesicle-microRNAs in Precapillary Pulmonary Hypertension.","authors":"Olga Tura-Ceide, Julia Oto, Jeisson Osorio, David Hervás, Víctor I Peinado, Verónica Sánchez-López, Elena Arellano, Miquel Gratacós, Cristina Bonjoch, Yolanda Torralba, Isabel Blanco, Pilar Medina, Remedios Otero, Joan Albert Barberà","doi":"10.1165/rcmb.2024-0282LE","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0282LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555586","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":"Cell Surface RNA Expression Modulates Alveolar Epithelial Function.","authors":"Jubilant Kwame Abledu, Christopher J Herbst, Raphael Brandt, Alen Kocak, Pritam Ghosh, Jacob L Gorenflos López, Kevin Diestelhorst, Stephan Block, Christian Hackenberger, Oliver Seitz, Elena Lopez-Rodriguez, Cengiz Gökeri, Martin Witzenrath, Matthias Ochs, Wolfgang M Kuebler","doi":"10.1165/rcmb.2024-0284OC","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0284OC","url":null,"abstract":"<p><p>Glycosylated RNA (glycoRNA) has recently emerged as a novel constituent of the glycocalyx on cell surfaces, yet its biological functions remain largely unexplored. In this report, we present the first analysis of glycoRNA expression and functionality in alveolar epithelial cells. To this end, we optimized new techniques for the detection of glycoRNA on living cell surfaces and in cell membrane-associated RNA samples through in-gel imaging after labeling with fluorescent dye conjugates. Specifically, we used conjugation of Cy5-hydrazide following mild oxidation with sodium periodate for detection of total cell surface sialoglycoRNA. Conjugation of dibenzocyclooctyne-sulfo-Cy5 (DBCO-Sulfo-Cy5) in cells fed with tetraacetylated <i>N</i>-azidoacetyl-mannosamine (Ac₄ManNAz) or 6-azido-L-fucose (FucAz) detected <i>de novo</i> formed sialoglycoRNA or fucoglycoRNA, respectively. Finally, biotinylated lectins in combination with infrared dye-conjugated streptavidin were used to differentiate between specific glycosidic linkages. Comparisons across primary alveolar epithelial cells and different alveolar-epithelial like cell lines revealed a cell-type specific variation in glycoRNA abundance. Treatment of primary alveolar epithelial cells with an RNase cocktail reduced epithelial surface glycoRNA and was associated with a reduction in trans-epithelial electrical resistance and influenza A viral particle abundance. As such, the present work identifies glycoRNA as a novel component of the alveolar epithelial glycocalyx with potential relevance in epithelial barrier regulation and viral infection.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555583","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":"Will Stub1 Be the Next Target for Pulmonary Hypertension Therapy Development?","authors":"Yuanjun Shen","doi":"10.1165/rcmb.2025-0034ED","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0034ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555589","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":"A Novel Role for Platelet-Endothelial Crosstalk in Pulmonary Hypertension.","authors":"Li Hu, Feng Chen","doi":"10.1165/rcmb.2025-0044ED","DOIUrl":"https://doi.org/10.1165/rcmb.2025-0044ED","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555579","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":"MOTS-c Promotes Glycolysis via AMPK-HIF-1α-PFKFB3 Pathway to Ameliorate CPB-induced Lung Injury.","authors":"Zihao Shen, Peng Lu, Wanjun Jin, Ziang Wen, Yuanpu Qi, Xiangyu Li, Mingyu Chu, Xin Yao, Minchao Wu, Ao Wang, Xiao Zhang, Wei Wang, Meijuan Song, Xiaowei Wang","doi":"10.1165/rcmb.2024-0533OC","DOIUrl":"https://doi.org/10.1165/rcmb.2024-0533OC","url":null,"abstract":"<p><p>Cardiopulmonary bypass (CPB) is essential during cardiac surgeries but frequently leads to lung ischemia-reperfusion injury (LIRI), a significant contributor to postoperative complications. This study investigated the protective effects of MOTS-c, a mitochondrial-derived peptide, against LIRI-induced acute lung injury (ALI), emphasizing glycolytic reprogramming and ferroptosis in pulmonary microvascular endothelial cells (PMVECs). We hypothesized that MOTS-c exerts its protective effects by regulating glycolysis and suppressing ferroptosis via metabolic signaling pathways. We conducted a prospective, controlled trial involving 107 patients undergoing CPB, evaluating plasma concentrations of MOTS-c and inflammatory markers. MOTS-c levels were significantly reduced in patients with ALI. In vivo and in vitro experiments demonstrated that MOTS-c pretreatment alleviated LIRI by enhancing glycolytic flux, reducing oxidative stress, and suppressing ferroptosis in PMVECs. MOTS-c specially reinstated the expression of PFKFB3, an essential glycolytic enzyme, thus preserving cellular energy homeostasis and diminishing lipid peroxidation. The study further emphasized the involvement of the AMPK-HIF-1α signaling pathway in the protective benefits facilitated by MOTS-c. MOTS-c elevated phosphorylated AMPKα and HIF-1α expression, indicating a vital function for these pathways in enhancing glycolysis and antioxidant defenses. Genetic and pharmacological inhibition of PFKFB3 abrogated the protective effects of MOTS-c, thereby confirming the essential role of PFKFB3-mediated glycolysis in alleviating LIRI. Our research indicates that MOTS-c could serve as a potential therapeutic agent for the prevention or treatment of LIRI-induced ALI by enhancing glycolysis, suppressing ferroptosis, and activating the AMPK-HIF-1α pathway. Future study should explore the clinical application of MOTS-c, potentially improving outcomes for patients undergoing high-risk cardiac operations.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539910","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":"A Single-Cell RNA Sequencing Atlas of the Chronic Obstructive Pulmonary Disease Distal Lung to Predict Cell-Cell Communication.","authors":"Jessica B Blackburn, Tiffany S Tufenkjian, Yang Liu, David S Nichols, Timothy S Blackwell, Bradley W Richmond","doi":"10.1165/rcmb.2024-0232LE","DOIUrl":"10.1165/rcmb.2024-0232LE","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"332-335"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363998","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":"Multiple Neural Networks Originating from the Lateral Parabrachial Nucleus Modulate Cough-like Behavior and Coordinate Cough with Pain.","authors":"Mingtong Lin, Mingzhe Liu, Chuqin Huang, Shuirong Shen, Zhe Chen, Kefang Lai","doi":"10.1165/rcmb.2024-0084OC","DOIUrl":"10.1165/rcmb.2024-0084OC","url":null,"abstract":"<p><p>It has been reported that experimental pain can diminish cough sensitivity and that the lateral parabrachial nucleus (LPBN) coordinates pain with breathing, but whether the LPBN regulates cough-like behaviors and pain-induced changes in cough sensitivity remains elusive. We investigated the roles of LPBN γ-aminobutyric acidergic (GABAergic) and glutamatergic neurons in the regulation of cough sensitivity and its relationship with pain in mice via chemogenetic approaches. Adenovirus-associated virus tracing combined with chemogenetics was used to map the projections of LPBN GABAergic and glutamatergic neurons to the periaqueductal gray. LPBN neurons were activated by cough challenge, and nonspecific inhibition of LPBN neurons suppressed cough-like behavior. Chemogenetic suppression of LPBN GABAergic neurons reduced cough sensitivity in mice, whereas suppression of LPBN glutamatergic neurons counteracted the pain-driven decrease in cough sensitivity, and so did silencing LPBN glutamatergic neurons projecting to the periaqueductal gray. Our data suggest that GABAergic and glutamatergic neurons in the LPBN critically are involved in cough sensitivity and coordinate pain with cough through inhibitory or activating mechanisms at the midbrain level.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"272-284"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455965","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":"Nicotine-Induced Endoplasmic Reticulum Stress and Airway Smooth Muscle Cell Proliferation Is Mediated by α7nAChR and Chaperones-RIC-3 and TMEM35.","authors":"Niyati A Borkar, Michael A Thompson, Brian Kelley, Barnabas T Shiferaw, Samantha K Hamrick, Venkatachalem Sathish, Y S Prakash, Christina M Pabelick","doi":"10.1165/rcmb.2024-0194OC","DOIUrl":"10.1165/rcmb.2024-0194OC","url":null,"abstract":"<p><p>Nicotine exposure in the context of smoking or vaping worsens airway function. Although nicotinic acetylcholine receptors (nAChRs) are commonly thought to exert effects through the peripheral nervous system, we previously showed that airway smooth muscle (ASM) expresses them, particularly α7 subtype nAChR (α7nAChR), with functional effects on contractility and metabolism. However, the mechanisms of nAChR regulation and downstream effects in ASM are not fully understood. Using ASM cells from people without asthma versus people with mild to moderate asthma, we tested the hypothesis that nAChR-specific endoplasmic reticulum (ER) chaperones, resistance to inhibitors of cholinesterase 3 (RIC-3) and transmembrane protein 35A (TMEM35A) promote cell surface localization of α7nAChR with downstream influence on its functionality: effects exacerbated by inflammation. We found that mild to moderate asthma and exposure to proinflammatory cytokines relevant to asthma promote chaperone and α7nAChR expression in ASM. Downstream, ER stress was linked to nicotine/α7nAChR signaling, where RIC-3 and TMEM35 regulate nicotine-induced ER stress, intracellular Ca²⁺ regulation, and ASM cell proliferation. Overall, our data highlight the importance α7nAChR chaperones in mediating and modulating nicotine effects in ASM toward airway contractility and remodeling.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"297-307"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139032","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 Complex Immune Cell Composition and Cellular Interaction in the Alveolar Compartment of Patients with Acute Respiratory Distress Syndrome.","authors":"Shiqi Zhang, JanWillem Duitman, Antonio Artigas, Lieuwe D J Bos","doi":"10.1165/rcmb.2024-0176TR","DOIUrl":"10.1165/rcmb.2024-0176TR","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) is characterized by protein-rich edema due to alveolar-capillary barrier dysfunction caused by inflammatory processes. Currently, our understanding of the inflammatory response in patients with ARDS is mainly based on assessment of the systemic compartment and preclinical studies. Investigations into the intricate network of immune cells and their critical functions in the alveolar compartment remain limited. However, with recent improvements in single-cell analyses, our comprehensive understanding of the interactions between immune cells in the lungs has improved. In this review, we summarize the current knowledge about the cellular composition and interactions of different immune cell types within the alveolar space of patients with ARDS. Neutrophils and macrophages are the predominant immune cells in the alveolar space of patients with ARDS. Yet, all immune cells present, including lymphocytes, participate in complex interactions, coordinate recruitment, modulate the lifespan, and control apoptosis through various signaling pathways. Moreover, the cellular composition of alveolar immune cells is associated with the clinical outcomes of patients with ARDS. In conclusion, this synthesis advances our understanding of ARDS immunology, emphasizing the crucial role of immune cells within the alveolar space. Associations between cellular composition and clinical outcomes highlight the significance of exploring distinct alveolar immune cell subsets. Such exploration holds promise for uncovering novel therapeutic targets in ARDS pathophysiology, presenting avenues for enhancing clinical management and treatment strategies for patients with ARDS.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":" ","pages":"233-243"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387295","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":"March Highlights/Papers by Junior Investigators/NIH News.","authors":"","doi":"10.1165/rcmb.72i3RedAlert","DOIUrl":"https://doi.org/10.1165/rcmb.72i3RedAlert","url":null,"abstract":"","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":"72 3","pages":"iii-iv"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522239","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}