American journal of physiology. Cell physiology最新文献

{"title":"The role of glycolysis in inflammation.","authors":"Ethan T Dehantschutter, Cormac T Taylor","doi":"10.1152/ajpcell.00113.2026","DOIUrl":"https://doi.org/10.1152/ajpcell.00113.2026","url":null,"abstract":"<p><p>A characteristic feature of inflamed tissue is hypoxia, which arises from elevated oxygen consumption and impaired perfusion. Inflammation is accompanied by metabolic reprogramming enabling immune and non-immune cells to meet increased bioenergetic and biosynthetic demands. Glycolysis is among the most ancient and fundamental metabolic pathways in biology. Hypoxia reduces mitochondrial oxidative phosphorylation, driving cells towards a reliance on glycolysis to sustain ATP production. This requires an increase in flux through the glycolytic pathway, which is mediated through rapid allosteric regulation of glycolytic enzymes, transcriptional upregulation of glucose transporters and glycolytic enzymes, and the formation of glycolytic enzyme complexes. In immune cells such as macrophages, neutrophils, and lymphocytes, enhanced glycolytic flux determines effector functions including, but not limited to, cytokine production, phagocytosis, migration, and antimicrobial activity, as well as maintaining bioenergetic homeostasis. Similarly, non-immune cells within inflamed tissues, including epithelial cells and stromal cells, utilize glycolysis to influence barrier function, tissue remodelling, and inflammation. In this review, we summarize our current understanding of how hypoxia drives glycolytic reprogramming during inflammation, examine the cell-type-specific impact of this, and discuss the therapeutic potential of targeting glycolytic pathways for inflammatory diseases.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855700","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":"Rethinking Holocrine Secretion: Functional Logic in Lipid-Producing Epithelia.","authors":"Marlon R Schneider","doi":"10.1152/ajpcell.00191.2026","DOIUrl":"https://doi.org/10.1152/ajpcell.00191.2026","url":null,"abstract":"<p><p>Holocrine secretion is typically described as an exception among glandular strategies, distinguished by cell disintegration and release of cellular fragments rather than vesicular contents. Yet this description treats holocrine glands primarily as anatomical curiosities and leaves their underlying biological logic largely unexplored. Here we propose that holocrine secretion can instead be understood as a differentiation program that couples lipid accumulation, terminal differentiation, and cell elimination. This design supports surface barrier function and points toward differentiation-based approaches for controlled epithelial cell removal.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855567","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":"Fluid shear regulation of local Ca²⁺ transients in right and left rat atrial myocytes under normal and increased beating rate.","authors":"Joon-Chul Kim, Kim Phuong Luong, Sun-Hee Woo","doi":"10.1152/ajpcell.00128.2026","DOIUrl":"https://doi.org/10.1152/ajpcell.00128.2026","url":null,"abstract":"<p><p>During volume increase or hemodynamic disturbances in the atrium, fluid shear and beating rate often increase. Shear stress induces Ca²⁺ waves in resting atrial myocytes. Here, we examined whether shear stress alters local Ca²⁺ signaling and how such shear adaptation changes with increased beating frequency in right atrial (RA) and left atrial (LA) myocytes. Using two-dimensional confocal Ca²⁺ imaging in combination with micro-puffing, we examined the spatiotemporal properties of junctional (peripheral) and non-junctional (central) Ca²⁺ signals in field-stimulated rat atrial myocytes. Shear stress (~16 dyn/cm²) immediately enhanced Ca²⁺ transients, with a larger effect in the center, followed by their inhibition. During the early stimulatory phase only, Ca²⁺ release and decay were prolonged, with greater lengthening in the periphery. Whereas no difference was observed between RA and LA shear responses at 1 Hz, larger stimulatory effects were observed in RA myocytes than in LA myocytes at 3 Hz, with no late inhibition. At 3 Hz, only RA myocytes showed early shear-induced prolongation of Ca²⁺ release in the periphery. Sarcoplasmic reticulum (SR) Ca²⁺ contents were similarly reduced by prolonged shear in both sides at 1- and 3-Hz. Increased frequency caused attenuations in Ca²⁺ transients and peripheral SR Ca²⁺ content in LA, but not RA, myocytes under control conditions. Our data suggest that shear stress transiently enhances central Ca²⁺ release during depolarization via prolonged peripheral release but later suppresses it, and that early shear-mediated Ca²⁺ release stimulation deteriorates more readily in LA myocytes at increased frequencies, partly due to a reduced peripheral store.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855507","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":"Fluid Restriction Enhances Mitochondrial Stress in Peripheral Blood Mononuclear Cells Following High-Volume Resistance Exercise in Health Young Males.","authors":"Hui-Ying Luk, Casey R Appell, Nigel C Jiwan, Heather L Vellers, Yasuki Sekiguchi, Danielle E Levitt","doi":"10.1152/ajpcell.00859.2025","DOIUrl":"https://doi.org/10.1152/ajpcell.00859.2025","url":null,"abstract":"<p><p>Exercising under dehydrated conditions is common among physically active individuals, yet its impact on immune cell mitochondrial quality control, oxidative stress and inflammatory signaling, and systemic inflammatory mediators remains poorly defined. This study investigated mitochondrial quality control and systemic inflammatory responses to high-volume resistance exercise (HVRE) under hydrated (HYD) and dehydrated (DEH) conditions in ten young men (21±1 years, 175±6 cm, 76.9±10.5 kg, 18.5±6.3% fat). Participants completed two identical HVRE sessions following either normal hydration or 24h fluid restriction. Peripheral blood mononuclear cells (PBMCS) collected before (PRE) and at 1h and 3h post-HVRE were analyzed for proteins related to mitochondrial quality control (PINK1, Parkin, DRP1, p-DRP1^S616, MFN2), oxidative stress and inflammatory signaling (p-NF-κB^S536, NF-κB, SOD2, H2O2), autophagy machinery and degradation (LC3-I, LC3-II, p62, cathepsin-L), and blood samples for systemic inflammatory mediators (IL-6, TNF-α, CRP, H₂O₂). Significant time × condition interaction effects revealed that LC3-II/I was greater in DEH than HYD at PRE and 3h. In DEH, LC3-II/I returned to PRE levels at 3h, whereas in HYD, it was greatest at 3h. PINK1 was greater at 1h and 3h and pDRP1^S616 was greater at 3h in DEH than HYD. Also, PINK1 and pDRP1^S616 were greatest at 3h post-HVRE in DEH. Lastly, significant condition main effects revealed greater MFN2, p62, LC3-II, H₂O₂ in PBMCs and greater IL-6, and CRP in serum in DEH than HYD. These results provide novel evidence that 24 hours of fluid restriction before metabolically demanding resistance exercise activates mitochondrial quality control in PBMCs and elevates systemic inflammatory mediators.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832305","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":"Identifying Quiescent Satellite Cells: A Scoping Review of Transcriptomic Markers and Limitations.","authors":"Anika L Syroid, Alexandra P Steele, Kevin A Murach, Thomas J Hawke","doi":"10.1152/ajpcell.00101.2026","DOIUrl":"https://doi.org/10.1152/ajpcell.00101.2026","url":null,"abstract":"<p><p>Skeletal muscle regeneration relies on the resident stem cell population, termed satellite cells. Mechanistically, understanding the quiescence and activation dynamics of muscle satellite cells are essential for regenerative therapies and emerging applications such as cellular agriculture. Quiescent satellite cells (QSCs) are typically identified by expression of PAX7 and functional characteristics including a lack of proliferation. However, with the rapidly growing body of transcriptomic data, there is a lack of consensus regarding what markers can be used to identify quiescent satellite cells across transcriptomic studies. The purpose of this review was to evaluate the transcripts currently used to identify QSCs using transcriptomics and to establish an evidence-based foundation that could be used for future analyses. After surveying published single-cell transcriptomic studies, we identified <i>Pax7</i> and/or <i>Myf5</i> as the most used markers of general satellite cell identity, while <i>Spry1</i>, <i>Cd34</i>, and <i>Calcr</i>, together with the absence of <i>Myod1</i>, <i>Mki67</i>, and <i>Cdk1</i> were most commonly used to identify QSC clusters in murine studies. In contrast, there is currently insufficient literature to make a confident conclusion on quiescence markers in larger mammals, including humans, pigs, and cattle. We also highlight the conceptual and technical challenges associated with transcriptomic analysis of satellite cell subpopulations, including continuum-based cell states, isolation induced transcriptional changes, and inconsistent terminology. As a field, greater consistency in language, standardized analyses, and cross-species validation will be required to progress the study of satellite cell quiescence and its translational utility.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832333","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":"Distinct P2 receptors initiate intracellular signaling involved in mechanotransduction in tenocytes.","authors":"Ryan E Armstrong, Mayeesha N Khan, Matthew W Grol","doi":"10.1152/ajpcell.00616.2025","DOIUrl":"10.1152/ajpcell.00616.2025","url":null,"abstract":"<p><p>Tendons adapt to mechanical load through mechanotransduction, but the molecular mechanisms underlying this process have not been fully elucidated. In other musculoskeletal tissues, purinergic (P2) receptors-activated by extracellular nucleotides released during mechanical stress-are critical regulators of cellular responses. Here, we investigated whether similar P2 signaling pathways are present in tendons. We show that primary tenocytes express several P2 receptors, including P2X4, P2Y₂, and P2Y₆. Live-cell imaging revealed that both ATP and UTP trigger transient intracellular calcium (Ca²⁺) signaling via P2Y₂. Surprisingly, only ATP significantly increased expression of mechanosensitive cytokines [interleukin 6 (<i>Il6</i>), prostaglandin-endoperoxide synthase 2 (<i>Ptgs2</i>)] and the tendon-specific transcription factor scleraxis (<i>Scx</i>), suggesting that additional P2 receptors contribute to ATP-driven gene regulation. Using bulk RNA-sequencing (RNA-seq), we performed the first unbiased, genome-wide analysis of early transcriptional responses to extracellular nucleotide stimulation in tenocytes. Transcriptomic profiling revealed that ATP selectively activates gene programs linked to inflammation and immune responses, whereas both ATP and UTP regulate genes associated with cell differentiation, angiogenesis, metabolism, and responses to mechanical stimuli. Consistent with these findings, receptor-specific inhibition demonstrated that P2Y₂ and P2X4 both contribute to ATP-induced transcriptional changes, whereas broader P2 receptor inhibition completely abrogated ATP-driven gene expression, supporting redundant or convergent purinergic signaling in tenocytes. Together, these findings suggest that while P2Y₂ governs calcium dynamics, the broader purinergic signaling network, including P2Y₂, P2X4, and possibly others, serves as a central mediator of tenocyte mechanotransduction.<b>NEW & NOTEWORTHY</b> This study shows that appendicular and axial tenocytes express P2 receptors, including P2Y₂, P2Y₆, and P2X4. Nucleotides signal through Ca²⁺ via P2Y₂, while several P2 receptors, including P2Y₂ and P2X4, trigger transcriptome changes that influence inflammation, differentiation, and mechanical responses. Notably, this study characterizes early responses to exogenous ATP or UTP in a mammalian cell type using bulk RNA sequencing, providing valuable insights for future research.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1129-C1144"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430135","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":"Fibroblast specialization across microanatomy in a single-cell atlas of human Achilles tendon.","authors":"Carla J Cohen, Jolet Y Mimpen, Alina Kurjan, Claudia Paul, Shreeya Sharma, Lorenzo Ramos-Mucci, Chinemerem T Ikwuanusi, Ali Cenk Aksu, Tracy Boakye Serebour, Marina Nikolic, Kevin Rue-Albrecht, Christopher Gibbons, Duncan Whitwell, Tom Cosker, Steven Gwilym, Ather Siddiqi, Raja Bhaskara Rajasekaran, Harriet Branford-White, Adam P Cribbs, Philippa A Hulley, David Sims, Mathew J Baldwin, Sarah J B Snelling","doi":"10.1152/ajpcell.00838.2025","DOIUrl":"10.1152/ajpcell.00838.2025","url":null,"abstract":"<p><p>Tendons are transitional tissues linking muscle to bone, enabling locomotion and fine motor control. The cellular biology across the Achilles tendon unit is poorly understood, yet is critical for interpreting normal function and pathological changes across its microanatomically defined functional zones. We generated a spatially resolved transcriptomic atlas of adult (age 45-76) nontendinopathic human Achilles tendon, sampling the tendon-bone junction (enthesis), midbody, myotendinous junction, and adjoining muscle. Six fibroblast subtypes were identified, with distinct transcriptional profiles and spatial distributions, suggesting specialized functional roles across the tendon. Two dominant fibroblast types were specifically positioned in the tendon midsubstance and paratenon (vessel-rich region surrounding the tendon fibrils); other populations included perineural, myotendinous junction-specific, muscle-specific, and lining-layer fibroblasts. These findings demonstrate how cellular diversity across a transitional tissue may underlie microanatomical-specific roles. This atlas provides a foundation for understanding cellular functions across the tendon and adjoining muscle and will be essential for comparisons with diseased tissue, identifying pathogenic mediators and treatment targets for autoimmune and degenerative pathologies of the Achilles tendon.<b>NEW & NOTEWORTHY</b> We present the first spatially resolved single-cell atlas of the human Achilles tendon. By sampling across the microanatomy of the tendon from enthesis to muscle, we demonstrate changes in fibroblast composition across this transitional tissue. Distinct fibroblast subsets were discovered with specific transcriptomic signatures, and several were found in distinct spatial locations corresponding to putative functional roles in tendon and adjoining muscle. These findings demonstrate how cellular diversity across a transitional tissue may underlie microanatomical-specific roles.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1460-C1473"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147588935","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":"Publisher's note.","authors":"","doi":"10.1152/ajpcell.00197.2026_NOT","DOIUrl":"https://doi.org/10.1152/ajpcell.00197.2026_NOT","url":null,"abstract":"","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":"330 5","pages":"C1559"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832295","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":"Chasing the ghost in the code: highlighting the mystery of a rare genetic condition.","authors":"Eric Delpire","doi":"10.1152/ajpcell.00090.2026","DOIUrl":"10.1152/ajpcell.00090.2026","url":null,"abstract":"<p><p>Here, we recount the story of a remarkable young girl who demonstrated extraordinary courage and resilience while confronting significant health challenges over the span of 23 years. Her journey is a testament to her determination to survive and thrive despite overwhelming obstacles. We detail the investigative efforts aimed at associating her clinical symptoms with a specific membrane transporter: the Na-K-2Cl cotransporter-1 (NKCC1), which this laboratory has dedicated more than three decades to studying. The work summarized here covers experiments using patient-derived cells, cells engineered to express wild-type or mutant cotransporter, and genetically modified mice carrying this patient-specific alteration. It is illuminated by reports of other rare human deleterious mutations, and work done by us and others using NKCC1 knockout mouse models. During our studies, we uncovered details regarding the trafficking of NKCC1, shedding light on how the protein is transported and positioned to carry out its function in epithelial cells. Furthermore, our findings revealed that NKCC1 may play a role in energy metabolism, suggesting that its activity influences metabolic processes within affected tissues. Our investigations also underscored the involvement of NKCC1 in the development of the nervous system. In addition, we discuss the evidence found that intestinal dysfunction is linked to NKCC1 abnormalities and evidence showing an established link between the cotransporter and epithelial cell-mediated inflammation. This patient's story stands as a testament to perseverance and the importance of scientific inquiry in understanding rare genetic disorders.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1188-C1206"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patched controls cell cycle and tissue architecture in <i>Caenorhabditis elegans</i> gonad.","authors":"Johanna Kate Farley, Madeleine Schwalbe, Fredrik Forsberg, Aqilah Amran, Sandeep Gopal","doi":"10.1152/ajpcell.00486.2025","DOIUrl":"10.1152/ajpcell.00486.2025","url":null,"abstract":"<p><p>Hedgehog (Hh) signaling is essential for embryonic development and tissue homeostasis in organisms. However<i>, Caenorhabditis elegans</i> lacks canonical Hh signaling due to the absence of key components, such as smoothened (SMO) and obvious Hh ligands. Despite this, <i>C. elegans</i> retains Patched homologs, <i>ptc-1</i> and <i>ptc-3</i>, which have specialized independent functions. Although <i>ptc-1</i> is predominantly expressed in the germline and <i>ptc-3</i> in somatic tissues, we demonstrate that both genes are required to maintain germ cell populations and proper actin cytoskeletal architecture in the progenitor zone of the germline. Disruption of actin-encoding genes impairs germ cell S-phase and reduces the number of cells in the progenitor zone, indicating that cytoskeletal integrity is critical for maintaining the germline. Furthermore, defects observed upon loss of Patched function are linked to disruptions in cholesterol metabolism. We show that the phenotypes observed in the gonads due to dietary cholesterol changes can be modulated through Patched receptors. Together, our findings reveal a role for Patched receptors in regulating gonad architecture and germ cell development through cholesterol-sensitive functions, offering insights into how metabolic cues influence the organization of complex tissues.<b>NEW & NOTEWORTHY</b> In this study, we demonstrate how two hedgehog signaling pathway receptors influence germ cell development and reproduction. We identified the roles of Patched receptors in regulating germ cell maintenance, a process that is likely dependent on cholesterol homeostasis. Our findings reveal that dietary cholesterol levels impact Patched-driven germ cell behavior and gonad structure, highlighting the critical role of Patched in germline development.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1364-C1377"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580022","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}