American journal of physiology. Cell physiology最新文献

{"title":"Innate players in Th2 and non-Th2 asthma: emerging roles for the epithelial cell, mast cell, and monocyte/macrophage network.","authors":"Johanna Kotrba, Ilka Müller, Alexander Pausder, Aaron Hoffmann, Belinda Camp, Julia D Boehme, Andreas J Müller, Jens Schreiber, Dunja Bruder, Sascha Kahlfuss, Anne Dudeck, Sabine Stegemann-Koniszewski","doi":"10.1152/ajpcell.00488.2024","DOIUrl":"10.1152/ajpcell.00488.2024","url":null,"abstract":"<p><p>Asthma is one of the most common chronic respiratory diseases and is characterized by airway inflammation, increased mucus production, and structural changes in the airways. Recently, there is increasing evidence that the disease is much more heterogeneous than expected, with several distinct asthma endotypes. Based on the specificity of T cells as the best-known driving force in airway inflammation, bronchial asthma is categorized into T helper cell 2 (Th2) and non-Th2 asthma. The most studied effector cells in Th2 asthma include T cells and eosinophils. In contrast to Th2 asthma, much less is known about the pathophysiology of non-Th2 asthma, which is often associated with treatment resistance. Besides T cells, the interaction of myeloid cells such as monocytes/macrophages and mast cells with the airway epithelium significantly contributes to the pathogenesis of asthma. However, the underlying molecular regulation and particularly the specific relevance of this cellular network in certain asthma endotypes remain to be understood. In this review, we summarize recent findings on the regulation of and complex interplay between epithelial cells and the \"nonclassical\" innate effector cells mast cells and monocytes/macrophages in Th2 and non-Th2 asthma with the ultimate goal of providing the rationale for future research into targeted therapy regimens.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1373-C1383"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum for Fu et al., volume 327, 2024, p. C1219-C1235.","authors":"","doi":"10.1152/ajpcell.00085.2024_COR","DOIUrl":"https://doi.org/10.1152/ajpcell.00085.2024_COR","url":null,"abstract":"","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":"327 6","pages":"C1686-C1687"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging roles of ketone bodies in cardiac fibrosis.","authors":"Kellina Maduray, Jingquan Zhong","doi":"10.1152/ajpcell.00241.2024","DOIUrl":"10.1152/ajpcell.00241.2024","url":null,"abstract":"<p><p>Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition within the myocardium, poses a significant challenge in cardiovascular health, contributing to various cardiac pathologies. Ketone bodies (KBs), particularly β-hydroxybutyrate (β-OHB), have emerged as subjects of interest due to their potential cardioprotective effects. However, their specific influence on cardiac fibrosis remains underexplored. This literature review comprehensively examines the relationship between KBs and cardiac fibrosis, elucidating potential mechanisms through which KBs modulate fibrotic pathways. A multifaceted interplay exists between KBs and key mediators of cardiac fibrosis. While some studies indicate a profibrotic role for KBs, others highlight their potential to attenuate fibrosis and cardiac remodeling. Mechanistically, KBs may regulate fibrotic pathways through modulation of cellular components such as cardiac fibroblasts, macrophages, and lymphocytes, as well as extracellular matrix proteins. Furthermore, the impact of KBs on cellular processes implicated in fibrosis, including oxidative stress, chemokine and cytokine expression, caspase activation, and inflammasome signaling is explored. While conflicting findings exist regarding the effects of KBs on these processes, emerging evidence suggests a predominantly beneficial role in mitigating inflammation and oxidative stress associated with fibrotic remodeling. Overall, this review underscores the importance of elucidating the complex interplay between KB metabolism and cardiac fibrosis. The insights gained have the potential to inform novel therapeutic strategies for managing cardiac fibrosis and associated cardiovascular disorders, highlighting the need for further research in this area.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1416-C1432"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune system activation and cognitive impairment in arterial hypertension.","authors":"Stefanie Schreiber, Philipp Arndt, Lorena Morton, Alejandra P Garza, Patrick Müller, Katja Neumann, Hendrik Mattern, Marc Dörner, Jose Bernal, Stefan Vielhaber, Sven G Meuth, Ildiko R Dunay, Alexander Dityatev, Solveig Henneicke","doi":"10.1152/ajpcell.00219.2024","DOIUrl":"10.1152/ajpcell.00219.2024","url":null,"abstract":"<p><p>Chronic arterial hypertension disrupts the integrity of the cerebral microvasculature, doubling the risk of age-related dementia. Despite sufficient antihypertensive therapy in still a significant proportion of individuals blood pressure lowering alone does not preserve cognitive health. Accumulating evidence highlights the role of inflammatory mechanisms in the pathogenesis of hypertension. In this review, we introduce a temporal framework to explore how early immune system activation and interactions at neurovascular-immune interfaces pave the way to cognitive impairment. The overall paradigm suggests that prohypertensive stimuli induce mechanical stress and systemic inflammatory responses that shift peripheral and meningeal immune effector mechanisms toward a proinflammatory state. Neurovascular-immune interfaces in the brain include a dysfunctional blood-brain barrier, crossed by peripheral immune cells; the perivascular space, in which macrophages respond to cerebrospinal fluid- and blood-derived immune regulators; and the meningeal immune reservoir, particularly T cells. Immune responses at these interfaces bridge peripheral and neurovascular unit inflammation, directly contributing to impaired brain perfusion, clearance of toxic metabolites, and synaptic function. We propose that deep immunophenotyping in biofluids together with advanced neuroimaging could aid in the translational determination of sequential immune and brain endotypes specific to arterial hypertension. This could close knowledge gaps on how and when immune system activation transits into neurovascular dysfunction and cognitive impairment. In the future, targeting specific immune mechanisms could prevent and halt hypertension disease progression before clinical symptoms arise, addressing the need for new interventions against one of the leading threats to cognitive health.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1577-C1590"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional analysis of cancer cachexia: conserved and unique features across preclinical models and biological sex.","authors":"Francielly Morena, Ana Regina Cabrera, Ronald G Jones, Eleanor R Schrems, Ruqaiza Muhyudin, Tyrone A Washington, Kevin A Murach, Nicholas P Greene","doi":"10.1152/ajpcell.00647.2024","DOIUrl":"10.1152/ajpcell.00647.2024","url":null,"abstract":"<p><p>Studies suggest heterogeneity in cancer cachexia (CC) among models and biological sexes, yet examinations comparing models and sexes are scarce. We compared the transcriptional landscape of skeletal muscle across murine CC models and biological sexes during early and late CC. Global gene expression analyses were performed on gastrocnemius [Lewis lung carcinoma (LLC)], quadriceps (KPC-pancreatic), and tibialis anterior [Colon-26 (C26)-colorectal and <i>Apc^Min/</i>⁺] muscles across biological sexes. Differentially expressed genes (DEGs) were identified using an adj-<i>P</i> value of <0.05, followed by pathway and computational cistrome analyses. Integrating all controls, early and late stages of all models and sexes revealed up to 68% of DEGs and pathways were enriched at early and late CC, indicating a conserved transcriptional profile during CC development. Comparing DEGs and pathways within sexes and across models, in early CC, the transcriptional response was highly heterogeneous. At late stage, 11.5% of upregulated and 10% of downregulated genes were shared between models in males, whereas 18.9% of upregulated and 7% of downregulated DEGs were shared in females. Shared DEGs were enriched in proteasome and mitophagy/autophagy pathways (upregulated), and downregulation of energy metabolism pathways in males only. Between sexes, though the proportion of shared DEGs was low (<16%), similar pathway enrichment was observed, including proteasome and mitophagy at late-stage CC. In early CC, oncostatin M receptor (<i>Osmr</i>) upregulation was the only commonality across all models and sexes, whereas CLOCK and ARNTL/BMAL1 were predicted transcriptional factors associated with dysregulations in all three male models. This study highlights sex and model differences in CC progression and suggests conserved transcriptional changes as potential therapeutic targets.<b>NEW & NOTEWORTHY</b> This study is among the first to integrate and compare the skeletal muscle transcriptional landscape across multiple preclinical models and biological sexes. We highlight that <i>1</i>) early CC transcriptional changes are two-thirds conserved at late stages, <i>2</i>) DEGs are largely model and sex specific, and <i>3</i>) transcriptional factors including CLOCK and ARNTL/BMAL1, which influence early CC gene expression, might represent a global therapeutic target with a chance of efficacy across various cancer types.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1514-C1531"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional regulation of olfactory receptor OR51B5 by the TBX6.","authors":"Jiyun Roh, Wesuk Kang, Suhjin Yang, Dabin Choi, Taesun Park","doi":"10.1152/ajpcell.00464.2024","DOIUrl":"10.1152/ajpcell.00464.2024","url":null,"abstract":"<p><p>Olfactory receptors (ORs) are G protein-coupled receptors primarily expressed in olfactory tissue, facilitating the perception of odors. Interestingly, they have also been detected in nonolfactory tissues such as the skin, where they regulate processes like collagen synthesis. This study aimed to analyze the promoter of the OR family 51 subfamily B member 5 (OR51B5) and identify the transcription factors that bind to it to understand the potential regulatory mechanisms for OR51B5 expression. We examined the promoter region spanning 2,000 base pairs upstream of the transcription start site and conducted a deletion analysis, revealing that the core promoter encompasses the region from -153 to -111 base pairs. A luciferase assay using various candidate transcription factors showed that the overexpression or knockdown of T-Box Transcription Factor 6 (TBX6) significantly regulated OR51B5 promoter activity, whereas other candidate transcription factors had no significant effect. In addition, we validated TBX6 binding to the OR51B5 promoter using site-directed mutation and electrophoretic mobility shift assays, and chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR). This study is the first to uncover the role of TBX transcription factors in regulating OR gene expression in mammals, which may have implications for treating related disorders.<b>NEW & NOTEWORTHY</b> This study reveals that olfactory receptor OR51B5, primarily known for its role in olfaction, is significantly regulated by the transcription factor TBX6 in nonolfactory tissues. We demonstrate that TBX6 binding to the OR51B5 promoter modulates its activity, highlighting a novel regulatory mechanism for olfactory receptor expression, which could impact collagen synthesis and cell survival in human dermal fibroblasts.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1564-C1576"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ciliopathy organoid models: a comprehensive review.","authors":"Matylda Zofia Kuzinska, Sally Yuan-Yin Lin, Verena Klämbt, Philip Bufler, Milad Rezvani","doi":"10.1152/ajpcell.00343.2024","DOIUrl":"10.1152/ajpcell.00343.2024","url":null,"abstract":"<p><p>Cilia are membrane-bound organelles found on the surface of most mammalian cell types and play numerous roles in human physiology and development, including osmo- and mechanosensation, as well as signal transduction. Ciliopathies are a large group of, usually rare, genetic disorders resulting from abnormal ciliary structure or ciliary dysfunction that have a high collective prevalence. Autosomal dominant or recessive polycystic kidney disease (ADPKD/ARPKD), Bardet-Biedl-Syndrome, and primary ciliary dyskinesia (PCD) are the most frequent etiologies. Rodent and zebrafish models have improved the understanding of ciliopathy pathophysiology. Yet, the limitations of these genetically modified animal strains include the inability to fully replicate the phenotypic heterogeneity found in humans, including variable multiorgan involvement. Organoids, self-assembled three-dimensional cell-based models derived from human induced pluripotent stem cells (iPSCs) or primary tissues, can recapitulate certain aspects of the development, architecture, and function of the target organ \"in the dish.\" The potential of organoids to model patient-specific genotype-phenotype correlations has increased their popularity in ciliopathy research and led to the first preclinical organoid-based ciliopathy drug screens. This review comprehensively summarizes and evaluates current ciliopathy organoid models, focusing on kidney, airway, liver, and retinal organoids, as well as the specific methodologies used for their cultivation and for interrogating ciliary dysfunction.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1604-C1625"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the mechanisms of muscle fatigue: insights from the Marion J. Siegman Award Lectures.","authors":"Arthur J Cheng, Nathaniel J Andrews, Thomas J Hawke","doi":"10.1152/ajpcell.00620.2024","DOIUrl":"10.1152/ajpcell.00620.2024","url":null,"abstract":"","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1347-C1348"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements and future directions in <i>American Journal of Physiology-Cell Physiology</i>: a 2024 editorial update.","authors":"Liliana Schaefer","doi":"10.1152/ajpcell.00862.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00862.2024","url":null,"abstract":"","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":"327 6","pages":"C1681-C1685"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicle miR-206 improves chronic binge alcohol-mediated decreased myoblast differentiation in SIV-infected female macaques.","authors":"Brianna L Bourgeois, Eden M Gallegos, Danielle E Levitt, Peter J Bergeaux, Patricia E Molina, Liz Simon","doi":"10.1152/ajpcell.00290.2024","DOIUrl":"10.1152/ajpcell.00290.2024","url":null,"abstract":"<p><p>Alcohol misuse in people with human immunodeficiency virus (HIV) (PWH) and chronic binge alcohol (CBA) administration in simian immunodeficiency virus (SIV)-infected macaques are associated with increased physical frailty and impaired functional skeletal muscle mass, respectively. Previous studies by our group demonstrate that muscle-enriched microRNAs (myomiRs) are differentially expressed in skeletal muscle (SKM) from CBA-administered SIV-infected male macaques and their altered expression contributes to impaired differentiation of SKM stem cells or myoblasts. MicroRNAs can be transported in extracellular vesicles (EVs) to mediate numerous cellular responses through intercellular communication. The present study tested the hypothesis that EV-mediated delivery of miR-206 can ameliorate CBA-mediated decreases in myoblast differentiation. Myoblasts were isolated from SKM of female SIV-infected, antiretroviral therapy-treated macaques that received either CBA (2.5 g/kg/day, CBA/SIV) or water (VEH/SIV) for 14.5 mo. Myotube and myotube-derived EV myomiR expression, including miR-206, was lower in the CBA/SIV group. Overexpression of miR-206 decreased histone deacetylase 4 (<i>HDAC4</i>) and paired box 7 (<i>PAX7</i>) expression in myotubes and increased fusion index, a differentiation index, in CBA/SIV-derived myotubes. Similarly, EV-mediated delivery of miR-206 increased both fusion index and myotube density of CBA/SIV-derived myoblasts. These results support the potential therapeutic utility of EVs in delivering myomiRs to improve SKM stem cell differentiation.<b>NEW & NOTEWORTHY</b> Alcohol decreases skeletal muscle myoblast differentiation into myotubes, which is associated with decreased expression of microRNA-206. We show that delivering exogenous miR-206 in plasma-derived extracellular vesicles (EVs) to myoblasts derived from alcohol-administered animals increases myotube differentiation. These results support the potential therapeutic utility of EVs in delivering muscle-enriched microRNAs to improve skeletal muscle stem cell differentiation.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1626-C1637"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}