American journal of physiology. Cell physiology最新文献

{"title":"Inflammation in cancer cachexia: still the central tenet or just another player?","authors":"Noemi Iaia, Chiara Noviello, Maurizio Muscaritoli, Paola Costelli","doi":"10.1152/ajpcell.00808.2024","DOIUrl":"10.1152/ajpcell.00808.2024","url":null,"abstract":"<p><p>Cancer cachexia, a multifactorial syndrome characterized by body weight loss, muscle, and adipose tissue wasting, affects patients with cancer. Over time, the definition of cachexia has been modified, including inflammation as one of the main causal factors. Evidence has suggested that a range of proinflammatory mediators may be involved in the regulation of intracellular signaling, resulting in enhanced resting energy expenditure, metabolic changes, and muscle atrophy, all of which are typical features of cachexia. Physiologically speaking, however, inflammation is a response aimed at facing potentially damaging events. Along this line, its induction in the cancer hosts could be an attempt to restore the physiological homeostasis. Interesting observations have shown that cytokines such as interleukins 4 and 6 could improve muscle wasting, supporting the view that the same mediator may exert pro- or anti-inflammatory activity depending on the immune cells involved as well as on the tissue metabolic demand. In conclusion, whether inflammation is crucial to the occurrence of cachexia or just one contributor among others, is still unclear. Indeed, while inflammation is a trigger of cachexia, the alterations of energy and protein metabolism and of the hormonal homeostasis occurring in cachexia likely act as inflammatory stimuli on their own. Whether the causative role prevails over the compensatory one likely depends on the tumor type and stage, patient lifestyle, the presence of comorbidities, and the response to anticancer treatments paving the way to a holistic, personalized approach to cancer cachexia.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1837-C1852"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968176","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":"Unraveling the functional and molecular interplay between cellular senescence and the unfolded protein response.","authors":"Joëlle Giroud, Emilie Combémorel, Albin Pourtier, Corinne Abbadie, Olivier Pluquet","doi":"10.1152/ajpcell.00091.2025","DOIUrl":"https://doi.org/10.1152/ajpcell.00091.2025","url":null,"abstract":"<p><p>Senescence is a complex cellular state that can be considered as a stress response phenotype. A decade ago, we suggested the intricate connections between unfolded protein response (UPR) signaling and the development of the senescent phenotype. Over the past ten years, significant advances have been made in understanding the multifaceted role of the UPR in regulating cellular senescence, highlighting its contribution to biological processes such as oxidative stress and autophagy. In this updated review, we expand these interconnections with the benefit of new insights, and we suggest that targeting specific components of the UPR could provide novel therapeutic strategies to mitigate the deleterious effects of senescence, with significant implications for age-related pathologies and geroscience.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":"328 6","pages":"C1764-C1782"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961003","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":"Comprehensive evaluation and application of tissue clearing techniques for 3-D visualization of splenic neural and immune architecture.","authors":"Jianing Li, Letian He, Wenling Wang, Siyu Wang, Dan Zhang, Liyun Liang, Guangping Song, Yijian Zhang, Shaoqing Yu, Lei Wang, Qiuying Han, Shaoyi Huang, Sen Li, Haiqing Tu, Zengqing Song, Huaibin Hu, Huiyan Li, Yang Yang, Min Wu","doi":"10.1152/ajpcell.00084.2025","DOIUrl":"https://doi.org/10.1152/ajpcell.00084.2025","url":null,"abstract":"<p><p>As the largest secondary lymphoid organ, the spleen plays a crucial role in initiating and sustaining immune responses against blood-borne pathogens through antigen capture and delivery. It is innervated by both autonomic and sensory nerves, which allows for neural modulation of its immune responses. The intricate spatial structure and precise coordination between immune and neural components are essential for proper splenic function, necessitating three-dimensional (3-D) imaging to reveal its architecture. However, the dense fibrous capsule and exceptionally rich vasculature of the spleen pose significant challenges for achieving comprehensive 3-D visualization of the entire organ. Here, we systematically evaluated and compared five cutting-edge tissue clearing approaches-ImmuView, fast light-microscopic analysis of antibody-stained whole organs, small-micelle-mediated human organ efficient clearing and labeling (SHANEL), advanced clear, unobstructed brain imaging cocktails and computational analysis (advanced CUBIC), and clearing-enhanced 3-D microscopy-for their effectiveness in rendering the spleen transparent for multiplexed antibody staining and high-resolution 3-D imaging. Our results indicated that SHANEL provided the clearest visualization of essential splenic neural and immune components. Meanwhile, advanced CUBIC achieved the greatest labeling efficacy for immune cells, albeit with slightly reduced transparency. Importantly, our study marked the first application of these optimized protocols to human spleen tissue, successfully revealing the highly organized immune cell zones and neural networks with enhanced clarity. Notably, we identified the nociceptive sensory innervation within human spleen tissue for the first time. Collectively, these findings establish optimal imaging strategies for visualizing splenic immune cells and neural structure in both murine and human tissues, providing profound insights into the intricate neuroimmune interactions and their pivotal roles in the immune functions of the spleen.<b>NEW & NOTEWORTHY</b> This study systematically assessed five tissue-clearing techniques and optimized the conditions of each protocol to overcome the challenges of splenic 3-D imaging posed by its dense structure and high pigmentation. The results demonstrated SHANEL and advanced CUBIC as the optimal methods for 3-D visualization of diverse splenic immune and neural architecture, with which we successfully mapped splenic neuroimmune landscape and identified nociceptive nerves within the human spleen for the first time.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":"328 6","pages":"C1699-C1715"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960887","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":"Physical activity and other modifiers of extracellular matrix dynamics in healthy and diseased tendon tissue: Focus on in vivo techniques.","authors":"Benjamin Rosborg, Michael Kjaer, Ann Damgaard","doi":"10.1152/ajpcell.01042.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.01042.2024","url":null,"abstract":"<p><p>Tendons has traditionally been considered largely metabolically inert, and little research has focused on tendon matrix dynamics. In the last few decades, the study of tendon extracellular matrix dynamics in humans has progressed immensely as new methods have been employed to investigate long-term tissue remodeling and more acute changes in the turnover of extracellular matrix in tendon tissue. The number of human <i>in vivo</i> trials has increased, and new exciting fields of research in modifiers of tissue dynamics have advanced tendon research and provided new insight. This paper reviews the current knowledge of tendon extracellular matrix dynamics in healthy and diseased tissue. Further, we review the response of various factors such as loading, unloading, exogenous growth factors, and aging. Physical activity and growth factors stimulate protein synthesis in a minor fraction of the adult human tendon, whereas inactivity reduces synthesis and increases breakdown of proteins in tendon. The influence of physical activity level seems to surpass the impact of aging per se on tissue turnover in tendon. A comprehensive understanding of tendon tissue extracellular matrix dynamics and its adaptation to modifiers is crucial for establishing a foundation for tendon injury prevention, treatment, and rehabilitation.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075436","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":"Natural compounds and strategies for fighting against drug resistance in cancer: a special focus on phenolic compounds and microRNAs.","authors":"Nina Petrović, Ivana Z Matić, Tatjana Stanojković","doi":"10.1152/ajpcell.00428.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00428.2024","url":null,"abstract":"<p><p>Bioactive phytochemicals, phenolic compounds, terpenoids, and alkaloids, exert antioxidative, anti-inflammatory, antigenotoxic, and anticancer effects, simultaneously showing minimal or no toxicity on normal, healthy cells. Phytochemicals targeting various signaling pathways and multiple mechanisms underlying intrinsic and acquired multidrug resistance (MDR) in cancer cells make them invaluable tools for the development of novel strategies for fighting against anticancer drug resistance in different cancer types, which is one of the ultimate goals of modern oncology research. As MDR is described to be a simultaneous development of resistance to multiple drugs with different chemical structures, mechanisms of action, and targets it is not surprising that multiple factors, such as genetic and epigenetic changes, as well as non-coding RNAs, including microRNAs may significantly contribute to the development MDR in cancer cells, and its targeting and modulation of their expression to sensitize cells to treatment. This review implies that some natural compounds, such as curcumin, resveratrol, kaempferol, allicin, and quercetin have the potential to interact with highly oncogenic and/or proinflammatory miRNAs such as miR-21/155/663/146a significantly influencing the response to cancer therapy. The article aims to point out how natural compounds may be used accompanied by miRNAs mimics or miRNA inhibitors to treat specific cancer types and subtypes to overcome multidrug resistance. The main challenge is to determine the proper doses and concentrations of both, miRNAs and compounds.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075433","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":"Organ Fibrosis - Beyond Collagen I Expression Fibroblast Phenotype and Basement Membrane Proteins.","authors":"Rachel M Biggs, Amy D Bradshaw","doi":"10.1152/ajpcell.00077.2025","DOIUrl":"https://doi.org/10.1152/ajpcell.00077.2025","url":null,"abstract":"<p><p>The prevalence of fibrotic disease and its contribution to organ failure has wide-ranging consequences in terms of both morbidity and mortality and is particularly relevant in chronic conditions that afflict aging populations. The paucity of treatment options for those with fibrosis-dependent complications illustrates the challenge and underlying complexity of controlling and reducing extracellular matrix (ECM) content once fibrosis has been established. Legitimately, a major focus of research in fibrosis has centered on transcriptional regulation of fibrillar collagen, particularly collagen I, and factors that induce the expression of genes encoding the fibrillar collagens. However, knowledge that other facets of extracellular matrix biology, in addition to fibrillar collagen content, also make significant contributions to fibrosis is appreciated with emerging significance. Herein, a summary of some recent advances in uncovering critical fibroblast activation states, ECM organization, and composition of fibrotic ECM including basement membrane components, are discussed. In addition, evidence in support of distinct fibroblast phenotypes in fibrotic tissues, that once established, limit regression of fibrosis despite alleviation of the initiating pathology, is given. As the capacity to reduce established fibrosis has the potential for profound translational significance across organs, more research into each of these important processes is merited.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962056","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":"Stromal heterogeneity in the adult lung delineated by single-cell genomics.","authors":"Tatsuya Tsukui, Dean Sheppard","doi":"10.1152/ajpcell.00285.2025","DOIUrl":"https://doi.org/10.1152/ajpcell.00285.2025","url":null,"abstract":"<p><p>Stromal cells in the lung provide structural support to other cells and play critical roles in inflammation, repair, and fibrosis after injury. Recent technological advancements in single-cell genomics have tremendously improved our knowledge of stromal heterogeneity in the lung. Stromal heterogeneity in single-cell RNA sequencing data is often conserved across different studies despite the different annotation strategies. Spatial analyses suggest that each stromal subset is characterized by unique anatomical locations in the adult lung. This review overviews the stromal heterogeneity delineated by single-cell RNA sequencing studies and highlights the functional characteristics and locations of each population.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966276","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":"Prolactin maintains the neonatal phenotype of enterocytes during lactation in newborn mice.","authors":"José Luis Dena-Beltrán, Ana Luisa Ocampo-Ruiz, Dina I Vázquez-Carrillo, Ericka A De Los Ríos, Xarubet Ruiz-Herrera, Magali Valle-Pacheco, Sairi Izchel Robles-Torres, Gonzalo Martínez de la Escalera, Carmen Clapp, Yazmín Macotela","doi":"10.1152/ajpcell.00981.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00981.2024","url":null,"abstract":"<p><p>After birth, the intestine experiences a gradual maturation process that transforms the gut epithelium to adapt to the changing feeding conditions, from maternal milk to solid food. Milk components regulate this transition from neonatal- to adult-type enterocytes. Prolactin (PRL), a hormone present in milk at high concentrations, regulates the metabolism of the nursing pups. However, the target tissues that mediate its actions are unknown. Here, we hypothesized that milk PRL influences the transition from neonatal- to adult-type enterocytes. We found that PRL and PRL receptors are present in the intestinal epithelium (IE) of neonatal mice where PRL exerts direct actions. PRL activated the AKT and ERK1/2 signaling pathways in intestinal epithelial cells in culture from PD10-12 neonatal mice, and spheroids derived from neonatal intestine proliferate in response to PRL. Moreover, at PD14, the intestine villi length, crypt depth and number are increased in PRL receptor null mice (<i>Prlr^-/-</i>), suggesting an accelerated maturation phenotype in the absence of PRL signaling. Also, <i>Prlr^-/-</i> mice showed decreased expression of neonatal IE markers and increased expression of adult-type IE markers. Consistently, the activity of lactase and the levels of the IgG transporter FcRn were reduced in the intestine of <i>Prlr^-/-</i> nursing pups. In summary, lack of PRL signaling promotes precocious intestinal enterocyte maturation, which may lead to adverse health consequences such as poor digestion of lactose and reduced passive immunity. By restraining intestinal maturation, PRL helps maintain the neonatal enterocyte phenotype needed to promote the optimal use of milk components in the nursing offspring.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963788","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":"Insulin potentiates mechanical responses in small dorsal root ganglion neurons by increasing the sensitization of TRPV4 channels.","authors":"Ayumi Fukazawa, Amane Hori, Juan A Estrada, Han-Kyul Kim, Norio Hotta, Gary A Iwamoto, Scott A Smith, Wanpen Vongpatanasin, Masaki Mizuno","doi":"10.1152/ajpcell.00255.2025","DOIUrl":"https://doi.org/10.1152/ajpcell.00255.2025","url":null,"abstract":"<p><p>We have previously reported that insulin potentiates the response to mechanical stimuli in small dorsal root ganglion (DRG) neurons. However, the mechanisms underlying the insulin-induced potentiated responsiveness to mechanical stimulation in sensory neurons remain unclear. Transient receptor potential vanilloid 4 (TRPV4) is expressed as a mechanosensitive channel in DRG neurons and is activated by mechanical stimuli. We therefore hypothesized that insulin augments the response to mechanical stimulation in small DRG neurons by enhancing sensitization of TRPV4 channels. Co-localization of TRPV4, insulin receptor (IR) and the C-fiber marker peripherin in small DRG neurons was evaluated by immunofluorescence demonstrating 53 ± 10 % of TRPV4-positive small DRG neurons were co-localized with IR and peripherin. In <i>in vitro</i> whole-cell patch clamp recordings from cultured DRG neurons, mechanically-activated currents were significantly increased 5 min after the application of insulin (P = 0.0137) and such augmentation was suppressed by TRPV4 antagonist HC067047. We further examined the impact of insulin on expression of the IR signaling pathway proteins in cultured DRG neurons using western blotting. Akt was significantly increased in cultured DRG neurons incubated with insulin (phospho-Akt: P = 0.0007, phospho/total Akt ratio: P = 0.0183). Furthermore, blocking IR signaling kinases, phosphoinositide 3-kinase (PI3K) and PKC, suppressed the insulin-induced augmentation in TRPV4 agonist-induced currents (PI3K: P = 0.0074, PKC: P = 0.0028). Collectively, our results suggest that insulin-induced potentiation of mechanical response in small DRG neurons occurs through enhanced sensitization of TRPV4 channels.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959996","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":"Sixteen Weeks of High-Speed Treadmill Running is Insufficient to Induce Achilles Tendinopathy in a Rat Model.","authors":"Snehal S Shetye, Margaret K Tamburro, Ashley K Fung, Thomas P Leahy, Madison N Magee, Harina A Raja, Stephanie N Weiss, Courtney A Nuss, Daniel C Farber, Louis J Soslowsky","doi":"10.1152/ajpcell.00186.2025","DOIUrl":"https://doi.org/10.1152/ajpcell.00186.2025","url":null,"abstract":"<p><p>Despite the high prevalence of Achilles tendinopathy, clinically-relevant animal models of Achilles tendinopathy are lacking. Previous studies have demonstrated possible tendinopathic cell and matrix changes with high-speed treadmill running, but the consistency as well as functional and mechanical consequences of these changes were unclear. We sought to determine the applicability of this protocol as a tendinopathy model by defining changes in Achilles tendon structure, function, and mechanics associated with 16 weeks of high-speed treadmill running (26.8 m/min, 60 min/day, 5 days/week). We expected high-speed running would induce detrimental structural, functional, and mechanical changes that worsen over the course of the 16-week protocol. Treadmill running did influence bodyweight, hindlimb gait, and tendon cross-sectional area. However, contrary to our hypothesis, treadmill running did not induce tendinopathic changes in matrix organization, cell morphology, or tendon mechanics. As such, alternative strategies for robust and reproducible induction of Achilles tendinopathy in pre-clinical animal models are needed.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966275","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}