American journal of physiology. Cell physiology最新文献

{"title":"Vascular protection by young circulating extracellular vesicles ameliorates aging-related pulmonary fibrosis.","authors":"Fiorenza Gianì, Benjamin B Roos, Patrick A Link, Bharath Somasundram, Sara R Dresler, Enrico Sciacca, Carlo Vancheri, Naureen Javeed, Giovanni Ligresti, Daniel J Tschumperlin, Nunzia Caporarello","doi":"10.1152/ajpcell.00022.2025","DOIUrl":"10.1152/ajpcell.00022.2025","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a fatal, aging-related disease characterized by aberrant lung remodeling and progressive scarring, leading to organ failure and death. Current FDA-approved antifibrotic treatments are unable to reverse established disease, highlighting the need for innovative therapeutic approaches targeting novel pathways and cell types. Mounting evidence, including our own, has recently highlighted the pathogenic role of aging-related endothelial abnormalities, including vascular inflammation and oxidative stress, in the progression of lung fibrosis, offering new therapeutic opportunities to block IPF progression. Unexplored, however, are the modalities to restore vascular abnormalities associated with progressive lung fibrosis, representing a critical gap to effective treatments for IPF. In this study, we demonstrate that circulating extracellular vesicles (cEVs) isolated from young mice are capable of reversing the aging-associated transcriptional alterations of the pulmonary vasculature, reducing transcripts associated with innate immunity, oxidative stress, and senescence, while simultaneously increasing transcripts linked to endothelial identity. Using the bleomycin model of persistent lung fibrosis in aged mice, we then demonstrate that pretreatment with cEVs improves the vascular response to injury and attenuates lung fibrosis progression, as demonstrated by reduced lung collagen content and preserved vascular network and lung architecture. These findings support the efficacy of interventions targeting endothelial aging-associated transcriptional alterations, such as young cEV delivery, in mitigating pulmonary fibrosis progression in animal models of persistent fibrosis and indicate the potential benefits of combined therapies that simultaneously address vascular and nonvascular aspects of IPF.<b>NEW & NOTEWORTHY</b> This study demonstrates that circulating extracellular vesicles (cEVs) isolated from young mice reverse the transcriptional alterations of the aged mouse pulmonary vasculature, leading to a more youthful endothelial transcriptional phenotype. As a result of this vascular phenotype, aged mice are protected from bleomycin-induced pulmonary fibrosis. These findings highlight the therapeutic potential of targeting vascular aging to alleviate pulmonary fibrosis.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C159-C169"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136210","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":"Organoid models for chemosensing cell studies.","authors":"Peihua Jiang, Nancy E Rawson","doi":"10.1152/ajpcell.00047.2025","DOIUrl":"10.1152/ajpcell.00047.2025","url":null,"abstract":"<p><p>Over the past decade, tremendous progress has been made in using organoids-three-dimensional, miniature organ-like structures-to model tissues and organs in vitro, including both regenerative tissues (which contain tissue-residing stem/progenitor cells) and largely nonregenerative tissues, such as the brain. Organoids resemble the tissues from which they are derived in many aspects of structure, function, and organization. As a result, organoid models have been used in a variety of fields for cell studies. Many well-written reviews have provided in-depth descriptions of organoid models for various systems. In this article, we review the establishment and application of tissue stem/progenitor cell-derived organoid models relevant to chemosensory cell studies (taste and smell) and discuss the limitations and future directions of using these models to study chemosensation.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C136-C144"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144232947","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":"Automated patch clamp analysis of heterologously expressed Kir6.2/SUR1 and Kir6.1/SUR2B K_ATP currents.","authors":"Kangjun Li, Vaishali Satpute Janve, Jerod S Denton","doi":"10.1152/ajpcell.00266.2025","DOIUrl":"10.1152/ajpcell.00266.2025","url":null,"abstract":"<p><p>ATP-sensitive potassium (K_ATP) channels are therapeutic targets for numerous metabolic, cardiovascular, and neurological disorders. Drug development for K_ATP channels requires electrophysiology assays for detailed compound characterization. Parallel automated patch clamp (APC) techniques offer considerable advantages over low-throughput manual patch clamp electrophysiology. Here, we characterized the functional properties and pharmacological sensitivity of heterologously expressed Kir6.2/SUR1 and Kir6.1/SUR2B using a SyncroPatch 384PE APC instrument. Ruptured-membrane and perforated-patch whole cell recordings in potassium fluoride and fluoride-free assay buffers and electrophysiology chips were evaluated for both subtypes. Effects of internal ATP and ADP, and magnesium (Mg²⁺) addition were also assessed. Kir6.2/SUR1 currents were constitutively active in all potassium fluoride-based recordings, insensitive to activation by the SUR1 agonist, VU0071063, and variably inhibited by glibenclamide. Success rates, current rundown, and glibenclamide sensitivity were associated with internal buffer composition. Recordings in fluoride-free buffers revealed a minor population of constitutively active Kir6.2/SUR1 currents and a larger population of currents exhibiting low basal activity and activation by VU0071063. Success rate and stability were associated with internal buffer composition. Kir6.1/SUR2B currents, which were most readily assayed in ruptured-membrane and potassium fluoride-based conditions, were stable, activatable with pinacidil, and inhibited by glibenclamide. Our study sheds new light on the behavior of Kir6.2/SUR1 and Kir6.1/SUR2B currents under available APC conditions and represents an important step toward developing truly high-throughput APC techniques for K_ATP.<b>NEW & NOTEWORTHY</b> Highly parallel automated patch clamp (APC) methods have revolutionized the way electrophysiology is performed in the pharmaceutical and biotechnology industries and increasingly in academic laboratories. Here, we characterized the functional and pharmacological properties of heterologously expressed Kir6.2/SUR1 and Kir6.1/SUR2B using a SyncroPatch 384PE APC instrument. The results of our studies highlight heretofore unappreciated effects of fluoride-base internal solutions on Kir6.2/SUR1 and provide foundational support for developing truly high-throughput electrophysiology methods for both drug targets.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C82-C92"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224025","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":"Sodium/hydrogen exchanger 8 affects sheet migration of human intestinal epithelial cells (HT29MTX) by influencing the actin cytoskeletal rearrangement.","authors":"Ju Wang, Christian Stock, Azam Salari, Ursula E Seidler, Katerina Nikolovska","doi":"10.1152/ajpcell.00826.2024","DOIUrl":"10.1152/ajpcell.00826.2024","url":null,"abstract":"<p><p>The gastrointestinal Na⁺/H⁺ transporter 8 (NHE8) is downregulated in the mucosa of patients with ulcerative colitis, and its deletion in the murine intestine causes a \"colitis-like\" phenotype. Since ulcerative colitis is characterized by repeated mucosal injury, we investigated the role of NHE8 in intestinal wound repair, by accessing its effect on intracellular pH (pH_i) regulation, cell proliferation, and migration. NHE8 expression was downregulated via shRNA lentiviral transduction in HT29MTX cells. The selected clonal cell line (HT29/shNHE8) with ∼80% reduced NHE8 mRNA expression displayed an increased proliferative but reduced migratory rate compared with the mock-transduced cells (HT29/pLKO1). The wound front of the HT29/shNHE8 cells consisted of both migrating and nonmigrating cells, and pH_i measured in this segment displayed the following values: pH_i(HT29/pLKO.1) = 7.35, pH_i(HT29/shNHE8_migrating) = 7.27, and pH_i(HT29/shNHE8_nonmigrating) = 7.1. The migrating HT29/shNHE8 cells exhibited a significantly increased NHE activity compared with migrating mock-transfected and nonmigrating cells, which was abolished by pharmacological NHE3 inhibition. NHE3 localized to the wound front of HT29/shNHE8, but not to that of HT29/pLKO.1 cells. Cell flattening and lamellipodia development were observed at the wound front in HT29/pLKO.1 cells, whereas the HT29/shNHE8 cells formed tight actin bundles and retained their apical-basal architecture. RAC1 and Cofilin-1, required for the generation of actin-based membrane protrusions, were absent at the wound front of HT29/shNHE8 cells but were expressed in migrating HT29/pLKO.1 cells, where RAC1 partially colocalized with NHE8. The results show that NHE8 downregulation reduces the pH_i and leads to enhanced epithelial cell proliferation, but impairs migration likely due to altered actin polymerization.<b>NEW & NOTEWORTHY</b> The Na⁺/H⁺ exchanger 8 (NHE8) plays an important role in the regulation of intracellular pH_i, cell proliferation, and epithelial sheet migration in HT29MTX intestinal cells. NHE8 knockdown cells lack the ability to dynamically rearrange the actin cytoskeleton at the wound front, resulting in a reduced migration rate. These observations provide insights into the molecular mechanism of the downregulation of this transporter in human ulcerative colitis and its role in epithelial restitution.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C50-C67"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155498","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":"Modulation of pain by ketones: a mini-review.","authors":"Lana L Heslop, Douglas E Wright","doi":"10.1152/ajpcell.00305.2025","DOIUrl":"10.1152/ajpcell.00305.2025","url":null,"abstract":"<p><p>Ketones, or ketone bodies, are organic molecules produced via ketogenesis in the liver in response to changing energy demands. Three ketones are generated that can act as metabolic messengers and a fuel source for the body, typically forming when glucose levels decrease within the bloodstream. A ketogenic diet, a form of low-carbohydrate, high-fat diet, stimulates ketogenesis and forces ketone utilization as an energy source by nonhepatic tissues. Currently, ketones, along with the ketogenic diet, have been of interest to many as a therapeutic mechanism for multiple conditions, including epilepsy, numerous neurodegenerative diseases, and diabetes. Emerging preclinical evidence suggests that ketones may play a powerful role in modulating acute and chronic pain. Here, we summarize the known benefits of ketones on neurological disease and nociceptive systems associated with pain. We discuss possible mechanisms identified from preclinical studies underlying the identified benefits of ketones in reducing pain.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C31-C37"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155497","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":"Activation of <i>ankrd1a</i> expression marks newly forming myofibers and regulates muscle cell differentiation in adult zebrafish skeletal muscle repair.","authors":"Mina Milovanovic, Mirjana Novkovic, Srdjan Boskovic, Rubén Marín Juez, Andjela Milicevic, Jovana Jasnic, Emilija Milosevic, Bojan Ilic, Didier Y R Stainier, Snezana Kojic","doi":"10.1152/ajpcell.00807.2024","DOIUrl":"10.1152/ajpcell.00807.2024","url":null,"abstract":"<p><p>Like mammals, zebrafish repair skeletal muscle through a multistep process that involves satellite cell activation, differentiation of progenitor cells into myocytes, their fusion into myotubes, followed by myotube maturation and myofiber hypertrophy. Coordination and timely regulation of these events are essential for functional muscle recovery. Here, we identify <i>ankrd1a</i>, a gene responsive to muscle stress, as a new player in the repair of adult zebrafish skeletal muscle and show its involvement in modulating molecular mechanisms behind myogenic cell differentiation. It is expressed in newly forming muscle fibers from the stage of myoblast-like cells to their differentiation into mature myofibers, as well as in the apparently intact muscle fibers that surround the injury. Loss of <i>ankrd1a</i> function alters regulatory pathways involved in muscle cell differentiation, contraction, and myocyte fusion, leading to the acceleration of myogenic differentiation. Our data point to <i>ankrd1a</i> as a novel marker of newly forming myofibers and a hallmark of the adaptive process occurring in the intact myofibers that are in contact with wounded tissue. Without affecting the main regulatory networks, <i>ankrd1a</i> fine-tunes skeletal muscle repair by preventing premature myogenic differentiation during injury repair, which itself could impair functional recovery.<b>NEW & NOTEWORTHY</b> This study identifies <i>ankrd1a</i> as a novel modulator of skeletal muscle repair in adult zebrafish. Revealing its dual role in newly forming and intact myofibers near injury, the work highlights <i>ankrd1a</i>'s function in fine-tuning myogenic differentiation during repair. We position <i>ankrd1a</i> as both a marker of myofibers that repopulate wounded tissue and a player in coordination of adaptive responses essential for effective muscle tissue recovery.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C213-C234"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214652","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":"Acute mitochondrial reactive oxygen species emissions drive mitochondrial dysfunction after traumatic muscle injury in male mice.","authors":"Junwon Heo, David L Miller, Jessica R Hoffman, Emma Oberholtzer, Katelyn M Castelli, Genevieve C Sparagna, Kelsey H Fisher-Wellman, Sarah M Greising, Jarrod A Call","doi":"10.1152/ajpcell.00407.2025","DOIUrl":"10.1152/ajpcell.00407.2025","url":null,"abstract":"<p><p>Volumetric muscle loss (VML) is characterized by contractile weakness, dysfunctional mitochondrial bioenergetics, and poor rehabilitation plasticity. A hyperpolarized mitochondrial membrane potential is one attribute of the dysfunction bioenergetics and can lead to excessive reactive oxygen species (ROS) emissions. The primary objective of this study was to define the role of acute ROS emissions after VML injury. Male C57BL/6J mice were randomized into experimental and control groups. A time course of ROS emissions and antioxidant buffering capacity (AoxBC) for VML-injured muscles was established across the first 60 days postinjury (dpi). SS-31, a mitochondrial-targeted peptide, was administered subcutaneously (8 mg/kg/day) for upto 14 dpi, and specific electron transport chain complex ROS emissions and mitochondrial bioenergetics were investigated. SS-31 and wheel running were combined in a regenerative rehabilitation model to determine whether attenuating acute ROS emissions improved adaptive capability of the remaining muscle. Lipidomic and proteomic analyses were conducted to explore mechanisms of SS-31 benefit after VML. ROS emissions were greater and AoxBC was less during the first 14 dpi and this was associated with dysfunctional mitochondrial bioenergetics regardless of carbohydrate or fat fuel substrate. Complexes I, II, and III were identified as the primary sources of ROS emissions. SS-31 attenuated ROS emissions at both 7 and 14dpi and led to greater mitochondrial respiratory conductance and efficiency out to 30 dpi. Regenerative rehabilitation did not produce greater contractile adaptations, but there was modest evidence of greater metabolic adaptations compared with rehabilitation alone. Lipidomic and proteomic analyses suggest that SS-31 contributes to redox protein abundance alterations after VML injury.<b>NEW & NOTEWORTHY</b> Volumetric muscle loss (VML) impairs mitochondrial bioenergetics, causing hyperpolarization, reduced respiratory conductance, and elevated reactive oxygen species (ROS). A mitochondrial-targeted peptide, SS-31, improved mitochondrial efficiency, lowered ROS, and boosted antioxidant buffering in VML-injured muscle. Combining SS-31 with rehabilitation slightly enhanced metabolism but not contractile function. This suggests oxidative stress is not the sole factor in contractile dysfunction after VML injury and underscores the need for multifaceted therapies to restore muscle after VML.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C235-C250"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224024","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":"Blebs regulate phosphoinositide distribution and promote cell survival through the Septin-SH3KBP1-PI3K axis.","authors":"Zifeng Zhen, Chunlei Zhang, Jiayi Li, Ling Liang, Congying Wu","doi":"10.1152/ajpcell.00096.2025","DOIUrl":"10.1152/ajpcell.00096.2025","url":null,"abstract":"<p><p>Cells rely on substrate adhesion to activate diverse signaling pathways essential for proliferation and survival. In the absence of proper adhesion to the extracellular matrix, cells undergo anoikis, a form of programmed cell death. Poorly attached cells often exhibit rounded morphology and form dynamic protrusions called blebs. Although the role of blebs in amoeboid migration is well-documented, recent studies have highlighted their role in anoikis resistance. However, little is known about whether the most abundant membrane components-phospholipids-function in blebs-facilitated anoikis resistance. Here, we report an enrichment of phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P₃] and a depletion of phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P₂] at bleb membrane, compared with nonbleb regions of the plasma membrane. Our results have shown that both PI(3,4,5)P₃ and PI(4,5)P₂ have restricted diffusion patterns between the bleb and nonbleb membrane regions. Subsequently, we reveal that phosphoinositide 3-kinase (PI3K) is recruited by SH3KBP1 via liquid-liquid phase separation and interacted with septin at the bleb necks. This Septin-SH3KBP1-PI3K axis then contributes to differential phosphoinositide (PI) distribution and anoikis resistance. These novel insights into PI dynamics and the associated molecular scaffolding not only elucidate the mechanisms of bleb formation and anoikis resistance but also highlight potential targets for therapeutic interventions in anchorage-independent cancers.<b>NEW & NOTEWORTHY</b> We reveal that bleb membranes are enriched in PI(3,4,5)P₃ but depleted in PI(4,5)P₂ compared with non-bleb regions. We find that the Septin-SH3KBP1-PI3K axis establishes differential phosphoinositide distribution, regulates phosphoinositide diffusion, and confers resistance to anoikis in detached tumor cells, providing novel targets to counteract anoikis resistance in cancer.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C145-C158"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186291","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":"Caspase-11 deficiency ameliorates elastase-induced abdominal aortic aneurysm in mice by suppressing inflammatory response of macrophages.","authors":"Shekhar Singh, Faxue Zhao, Linlin Fan, Wei Xin, Hao Liu, Guofu Zhu, Chong Xu, Dekui Zhang, Jinlin Tian, Imran Ibrahim Shaikh, Wenliang Che, Yawei Xu, Zuodong Song, Xiankai Li, Dongyang Jiang","doi":"10.1152/ajpcell.00716.2024","DOIUrl":"10.1152/ajpcell.00716.2024","url":null,"abstract":"<p><p>Abdominal aortic aneurysm (AAA) is a life-threatening, inflammation-related vascular disease lacking specific drugs. Murine caspase-11 (CASP11, its human orthologs CASP4/CASP5) is the major component of the noncanonical inflammasome. However, the role of CASP11 in AAA remains unknown. Using a modified mice model combining oral β-aminopropionitrile administration and periaortic elastase application, we observed the activation of CASP11 during the development of AAA. Genetic deletion of <i>Casp11</i> protected AAA development with an improved survival rate and ameliorated the destruction of vessel walls, compared with wild-type (WT) mice. Correspondingly, <i>Casp11</i> knockout (KO) aortas showed less infiltrated macrophages; lower expression levels of cytokines, including interleukin-1β, interleukin-6, and monocyte chemotactic protein 1; and reduced matrix metalloproteinase 9 activity. Myeloid CASP11 contributed dominantly to the protective effects analyzed by the bone marrow transplantation experiment. In vitro assay indicated that CASP11 was upregulated in proinflammatory M1 macrophages. To explore the mechanism, CD11b⁺F4/80⁺ macrophages were sorted by flow cytometry from the AAA tissues of WT and <i>Casp11</i> KO mice to perform RNA sequencing, and the bioinformatic analysis revealed the downregulation of various inflammatory processes in <i>Casp11</i>-deficient macrophages. Collectively, macrophage CASP11 has a critical role in the development of AAA, providing a potential therapeutic strategy for treating AAA disease.<b>NEW & NOTEWORTHY</b> This study identified macrophage-derived CASP11 as a critical mediator in vascular inflammation and a contributing factor to the progression of AAA using a knockout mouse model. Given that CASP11 is well-established as a cytoplasmic sensor for LPS from gram-negative bacteria, these findings provide valuable insights into the potential mechanisms by which colonizing gram-negative bacteria may influence the pathogenesis of AAA.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C93-C106"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214653","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":"The biodiversity of KS-proteoglycans in cellular regulation and tissue function: emerging bioregulatory roles for low sulfation proteoglycans and bioconjugates.","authors":"James Melrose","doi":"10.1152/ajpcell.00268.2025","DOIUrl":"10.1152/ajpcell.00268.2025","url":null,"abstract":"<p><p>The aim of this study was to illustrate the biodiverse properties of keratan sulfate (KS) proteoglycans (PGs), their varied functions in tissues, and emerging roles for low sulfation isoforms of KSPGs now detectable due to the development of some novel KS antibodies. KS is a glycosaminoglycan (GAG), of diverse structure and functional properties and decorates a large range of PGs and equips these with cell regulatory properties. KSPGs also have biophysical roles in tissue stabilization and specific roles in electroconductive bioregulation of neural processes controlling tissue functions. Compared with the multitude of studies on other GAGs, KS has been rather neglected. In the past, the major focus was on the biology of high charge density isoforms of KS. In the present day, the development of antibodies that can now detect low sulfation isoforms of KS have demonstrated their potential roles in novel cell regulatory processes adding to the diverse bioregulatory properties of KSPGs. KS and KSPGs are now entering new areas in bioregulation adding to the functional roles of PGs in the regulation of connective tissue form and function in health and disease.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C251-C271"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214654","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}