Acta Physiologica最新文献

{"title":"Renal Phosphate Reabsorption in Humans Depends on at Least Three Distinct Transporters Unlike in Mice","authors":"Ashley L. Fernandes,&nbsp;Laurine Lang,&nbsp;Jürgen Klar,&nbsp;Anja Giese,&nbsp;Alexander Ehrmann,&nbsp;Rupert Busch,&nbsp;Hannah Auwerx,&nbsp;Christoph Daniel,&nbsp;Nati Hernando,&nbsp;Isabel Rubio-Aliaga,&nbsp;Carsten A. Wagner","doi":"10.1111/apha.70271","DOIUrl":"10.1111/apha.70271","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Kidney excretion of phosphate is the gatekeeper of systemic phosphate homeostasis as evident from inborn and acquired diseases. Renal phosphate transporters are a promising target for phosphate-lowering drugs, but molecular details of human kidney phosphate handling are largely unknown. Here, we aim to understand the dependency of renal phosphate transport on species, age, and sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used a combination of transporter-specific inhibitors and radioactive flux measurements in isolated BBM vesicles prepared from human and murine kidneys. We included human female and male neonates (0–11 months) and adults (51–63 years) and age-matched mouse kidneys. Immunoblotting and immunofluorescence detected transport protein expression, and transcript expression was analyzed in publicly available data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>The flux experiments revealed that in human kidneys SLC34A1, SLC34A2/3 and other non-SLC34 transporter are active and expressed with age- and sex-dependent differences. In mice about 80% of renal phosphate handling depends on Slc34a1, but in humans SLC34A1 contribution is 60% in neonates and only 40% in adults. SLC34A3 contribution accounts for 20% in human neonates and 40% in human adults but is almost negligible in mice. Non SLC34 sodium-dependent phosphate transport was around 20% in all groups. SCRNA-seq data and immunoblotting analysis revealed differences in sodium cotransporters between species that supported the activity measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data provide the first direct measurement of sodium-phosphate cotransporter activities in human kidney and show profound differences between species. These results are critical when developing novel drugs to modulate renal phosphate reabsorption.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Under Control? Mouse Models of Heat Exposure: A Systematic Review of Experimental Design and Methodology","authors":"Amina H. Rhaman,&nbsp;Leaf R. Kardol,&nbsp;Shane K. Maloney,&nbsp;Ebony Quintrell,&nbsp;Elizabeth Sorial,&nbsp;Shannon Morgan,&nbsp;Danielle J. Russell,&nbsp;Erin Kelty,&nbsp;Caitlin S. Wyrwoll","doi":"10.1111/apha.70281","DOIUrl":"10.1111/apha.70281","url":null,"abstract":"<p>Mouse models are widely used to study heat-related physiological responses as they provide insights relevant to human health. However, species differences (including nocturnal behavior) and standard housing below the thermoneutral zone (TNZ; 26°C–34°C) can confound comparisons. This systematic review evaluates methodologies, including housing temperatures, used in mouse heat-exposure studies published over the past 4 years. Medline, Web of Science, and Embase were searched for peer-reviewed mouse heat-exposure studies published from 2020 to 10 January 2025. Data on housing temperature, heat-exposure protocols, and physiological outcomes were extracted. Screening and extraction were conducted independently and in duplicate in Covidence. One hundred seventy studies were included. Of those, 142 (83%) housed control mice below TNZ; seven (4%) studies maintained TNZ conditions and the remainder did not report control temperature. Heat exposures ranged from 30°C–45°C, most commonly 39°C–41°C. Body temperature was measured in 110 (65%) studies, often targeting ~42°C. When timing was reported, exposures occurred mainly during the light phase (52, 30%). Most studies used males only (116, 68%); 31 (18%) used females only; 9 (5%) included both sexes; and 14 (8%) did not report sex. Common outcomes were digestive (55, 32%), inflammatory (47, 28%), and central nervous system (40, 24%). Recent mouse heat-exposure studies often compare heat-exposed animals with cold-stressed controls and apply daytime exposures that conflict with the nocturnal behavior of mice and human diurnal pattern. Incomplete reporting of housing conditions limits interpretation. Future research should account for differences between mice and humans to improve translational relevance.</p><p><b>Trial Registration:</b> PROSPERO: CRD42024611316</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of Claudin-2 and Trpv6 Results in Hypocalcemia, Hypercalciuria, and Altered Bone Microarchitecture in Mice","authors":"Harneet Kaur Bhullar,&nbsp;Amanda Lima Deluque,&nbsp;Debbie D. O'Neil,&nbsp;Wanling Pan,&nbsp;Michael R. Doschak,&nbsp;Henrik Dimke,&nbsp;R. Todd Alexander","doi":"10.1111/apha.70279","DOIUrl":"10.1111/apha.70279","url":null,"abstract":"<p>Transepithelial calcium absorption occurs via a transcellular or paracellular pathway. The intestinal transcellular pathway relies, at least partially, on the apical calcium channel transient receptor potential vanilloid 6 (TRPV6), whereas paracellular calcium (re)absorption occurs through tight junction proteins, including claudin-2 (CLDN2). Both CLDN2 and TRPV6 are also expressed in the kidney. CLDN2 contributes to proximal tubular calcium reabsorption, whereas the functional relevance of TRPV6 remains unclear. <i>Cldn2</i>^{<i>−/−</i>} knockout mice exhibit reduced intestinal calcium permeability and hypercalciuria, while maintaining normal bone mineral density (BMD), plasma calcium, and calciotropic hormone levels. <i>Trpv6</i>^{<i>D541A/D541A</i>} pore mutants were reported to have normal urinary and plasma calcium levels, despite reduced intestinal calcium absorption on a low calcium diet. However, we found subtle sex-specific differences in calcium homeostasis in these mice. We hypothesized that transcellular and paracellular calcium absorption pathways compensate for one another in these models. To test this, we crossed <i>Cldn2</i>^{<i>−/−</i>} with <i>Trpv6</i>^{<i>D541A/D541A</i>} mice to generate a functional double knockout (DKO, <i>Cldn2</i>^−/−/<i>Trpv6</i>^D541A/D541A). These mice displayed hypocalcemia, elevated calcitriol, and reduced BMD. Surprisingly, despite unchanged fecal calcium excretion, renal calcium wasting was greater than in <i>Cldn2</i>^{<i>−/−</i>} mice. Gene expression studies revealed increased calbindin-D_9k expression in the proximal colon and calbindin-D_28k in the kidney, consistent with partial compensation by the colon and distal nephron. Together, these findings indicate that combined impairment of paracellular and transcellular calcium transport reduces intestinal and renal calcium (re)absorption, leading to hypocalcemia and increased calcitriol levels, and highlight a role for TRPV6 in distal nephron calcium handling.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2X7-NEK7-NLRP3 Axis Drives Cardiac Inflammation and Fibrosis in Isoproterenol-Induced Cardiac Remodeling in Mice","authors":"Aline Cristina Parletta,&nbsp;Gabriela Cavazza Cerri,&nbsp;Marina Fevereiro,&nbsp;Karine Panico,&nbsp;Claudia Ribeiro Borba Gasparini,&nbsp;Denival Nascimento Vieira-Junior,&nbsp;Amanda de Almeida Silva,&nbsp;Nathalia Senger,&nbsp;Gabriela Placoná Diniz,&nbsp;Patrícia Castelucci,&nbsp;Maria Cláudia Costa Irigoyen,&nbsp;Maria Luiza Morais Barreto-Chaves","doi":"10.1111/apha.70280","DOIUrl":"10.1111/apha.70280","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Cardiac remodeling (CR) is a critical risk factor for the development and progression of cardiovascular diseases. CR is accompanied by activation of the innate immune response, with NLRP3 inflammasome emerging as a key player in morphological and functional changes. However, the mechanisms underlying NLRP3 inflammasome assembly and activation in the heart upon beta-adrenergic overactivation remain poorly understood. This study aims to investigate the temporal profile of NLRP3 inflammasome activation and its upstream signaling P2X7-NEK7 in isoproterenol (ISO)-induced CR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Wild-type (WT), NLRP3 knockout (NLRP3-KO), and P2X7-KO male mice were treated with ISO (60 mg/kg) for 1 h, 12 h, 24 h, or 14 days. Cardiac function was assessed by echocardiography and plethysmography. Cardiac hypertrophy and fibrosis were evaluated by histology. Fibrosis markers and cytokines gene expression were analyzed by quantitative PCR. Protein expression was evaluated by Western Blotting. Inflammasome assembly was confirmed by ASC speck immunofluorescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>WT mice showed a rapid activation of NLRP3 inflammasome in the heart up to 12 h from ISO administration, evidenced by increased NLRP3, ASC speck, Caspase-1, and IL-1β. ISO treatment for 12 h also increased P2X7 and NEK7. NLRP3-KO mice were protected from ISO-induced fibrosis and impairment of LV relaxation as well as the Caspase-1 activation and cytokines production. NEK7, NLRP3 activation, and fibrosis were prevented in P2X7-KO. NLRP3 deletion did not affect ISO-induced cardiac hypertrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that the NLRP3 inflammasome is activated by the P2X7-NEK7 pathway in the early stage of beta-adrenergic insult, driving ISO-induced cardiac fibrosis and inflammation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148443520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitoquinone Prevents Cardiac Dysfunction by Normalizing Mitochondrial ROS and Calcium Handling in Acute Myocardial Infarction","authors":"Carolina Falcão Ximenes,&nbsp;Pietra Zava Lorencini,&nbsp;Carmen Castardeli,&nbsp;Marlon Ramos Rosado Machado,&nbsp;Katyana Kaline Silva Ferreira,&nbsp;Sara Bianca Oliveira Mendes,&nbsp;Anna Karolina Nascimento Costa,&nbsp;Mario Morais Silva,&nbsp;Sérgio Ricardo Aluotto Scalzo,&nbsp;Marcos Eliezeck,&nbsp;Silvia Guatimosim,&nbsp;Eduardo Hertel Ribeiro,&nbsp;Donald M. Bers,&nbsp;Aurélia Araujo Fernandes,&nbsp;Ivanita Stefanon","doi":"10.1111/apha.70276","DOIUrl":"10.1111/apha.70276","url":null,"abstract":"<p>Acute myocardial infarction (MI) is the leading cause of heart failure (HF). However, the role of mitochondrial ROS (ROSm) in early MI dysfunction remains unclear. This study aimed to evaluate the impact of MitoQ on cardiac function in cases of heart HF following MI. Male Wistar rats were divided into four experimental groups: Sham, Infarct, Sham+MitoQ, and Infarct+MitoQ. MitoQ was administered orally (8 mg/kg/dia) for 7 days. Hemodynamic parameters, infarct area, papillary muscle contractility, cardiomyocyte mechanics, Ca²⁺ transients, and total and mitochondrial superoxide (DHE and MitoSOX) were assessed. After 7 days of MI, rats exhibited impaired contractility, altered inotropic response to extracellular Ca²⁺, cardiomyocyte hypertrophy, and increased total and ROSm. MitoQ prevented body weight loss and significantly improved hemodynamic parameters compared to the Infarct group. In papillary muscles, MitoQ restored basal isometric force and the inotropic response to extracellular Ca²⁺. In cardiomyocytes, it attenuated hypertrophy, preserved shortening, and reduced ([Ca²⁺]i) transient amplitude. MitoQ significantly decreased total and mitochondrial O₂•⁻ production. It selectively reduced NOX1 expression under simulated conditions but did not significantly affect NOX2, SOD1, or catalase expression in the context of MI. MitoQ prevented contractile dysfunction, suggesting that mitochondrial oxidative stress plays a decisive role in myocardial dysfunction during the acute phase of MI. Targeting antioxidant therapy to the mitochondria represents a promising strategy for preventing post-infarction heart failure and opens new perspectives for the development of more effective interventions in the treatment of cardiovascular diseases.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70276","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148416929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Levetiracetam inhibits the Na+ HCO3− transporter Ncbe/NBCn2 (Slc4a10) in the choroid plexus of mice","authors":"Laura Øllegaard Johnsen,&nbsp;Lasse Messell Desdorf,&nbsp;Nicoline Stærke Jensen,&nbsp;Jeppe Praetorius,&nbsp;Helle Hasager Damkier","doi":"10.1111/apha.70275","DOIUrl":"10.1111/apha.70275","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The Na⁺-dependent Cl⁻/HCO₃⁻ exchanger Ncbe/NBCn2 (<i>Slc4a10</i>) constitutes a major basolateral HCO₃⁻ uptake pathway in the choroid plexus and contributes to cerebrospinal fluid secretion and pH regulation. This study examined whether levetiracetam inhibits Ncbe/NBCn2-mediated transport and alters cerebrospinal fluid acid–base balance, transporter abundance, and cerebrospinal fluid secretion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Ncbe and NBCn1 activity was assessed in heterologous expression systems as Na⁺-dependent pH recovery after intracellular acidification. Na⁺-dependent pH recovery was also measured in isolated mouse choroid plexus epithelial cells. Cerebrospinal fluid pH and apparent secretion rate were assessed in vivo after levetiracetam treatment. Acetazolamide was included as a pharmacological control for inhibition of HCO₃⁻-dependent secretion. Transporter abundance was assessed by immunoblotting, and molecular docking was used to explore interactions between levetiracetam, Ncbe and related <i>SLC4A</i> transporters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Levetiracetam inhibited Ncbe-mediated transport, whereas no levetiracetam-sensitive NBCn1-mediated component was detected under the same experimental conditions. In choroid plexus epithelial cells, levetiracetam reduced Na⁺-dependent pH recovery to a similar extent as pharmacological inhibition of stilbene-sensitive transport. After 5 days of treatment, levetiracetam was associated with lower cerebrospinal fluid pH and a higher apparent cerebrospinal fluid secretion rate compared with control mice. Levetiracetam reduced Ncbe and NBCe2 abundance, while aquaporin-1 abundance increased. Molecular docking predicted levetiracetam interactions with residues involved in Na⁺ and HCO₃⁻ coordination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings identify Ncbe as a levetiracetam-sensitive HCO₃⁻ transporter in the choroid plexus and support effects on cerebrospinal fluid acid–base balance and secretion.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70275","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148409803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Myopathic and Transcriptomic Changes in Soleus and Gastrocnemius Muscles in a Novel Chronic Hindlimb Ischemia Rat Model Induced by Endovascular Catheter Occlusion","authors":"Oliver Kitzerow,&nbsp;Zhiqiu Xia,&nbsp;Samuel Gillman,&nbsp;Iraklis I. Pipinos,&nbsp;Han-Jun Wang","doi":"10.1111/apha.70278","DOIUrl":"10.1111/apha.70278","url":null,"abstract":"<p>Peripheral artery disease (PAD) is a progressive atherothrombotic disorder affecting more than 230 million people worldwide. Conventional animal models of chronic hindlimb ischemia (HLI) are highly invasive, technically challenging, fail to account for anatomical variation, and may not accurately recapitulate progressive PAD pathophysiology. To address these limitations, we developed a novel chronic HLI model using an ilio-femoral endovascular catheter occlusion (IFCO) approach. We hypothesized that IFCO would chronically reduce hindlimb blood flow, induce PAD-associated myopathy, and overcome limitations of conventional techniques. Laser Doppler perfusion imaging demonstrated that IFCO reduced resting hindlimb perfusion by 70%, with significant reductions persisting for up to 28 days. Histological analysis of the soleus revealed significantly increased fibrosis (4.99% in sham vs. 13.19% in IFCO) and reduced myofiber cross-sectional area (3072.21 μm² in sham vs. 1556.27 μm² in IFCO), whereas no significant differences were observed in the gastrocnemius. In contrast, IFCO increased the proportion of centralized nuclei from near 0% in sham muscles to 21.55% in the gastrocnemius and 32.65% in the soleus. RNA sequencing corroborated these findings and demonstrated that the ischemic soleus transcriptome exhibited enhanced fibrotic, pro-angiogenic, and myoblast fusion-associated signaling consistent with histological evidence of myopathy. These findings demonstrate that IFCO produces sustained hindlimb ischemia and PAD-associated skeletal muscle remodeling, with distinct responses between muscle types. This model may facilitate studies of PAD-associated myopathy and support the development of targeted therapeutic interventions.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70278","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148416919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Turkish Society of Physiological Sciences, 50th Turkish Physiology Congress, 12–16 November 2025, Antalya, Türkiye”","authors":"","doi":"10.1111/apha.70268","DOIUrl":"https://doi.org/10.1111/apha.70268","url":null,"abstract":"<p>\u0000 “ <span>Supplement: Turkish Society of Physiological Sciences, 50th Turkish Physiology Congress, 12–16 November 2025, Antalya, Türkiye</span>,” <i>Acta Physiologica</i> <span>242</span>, no. <span>S736</span> (<span>2026</span>).\u0000 </p><p>In the originally published version of this abstract the Symposia session ended at page 17. The addition of the Symposia session pages resulted in repagination. This has now been corrected in the online version.</p><p>In Abstract OC-33, “Effects of Phoenixin-14 Administration on AMPK, JAK2/STAT3, Sema 3E Signaling Pathways in Isoproterenol-Induced Myocardial Infarction Rats,” the author's name has been corrected from Fatih Akar to Fatih Kar.</p><p>We apologize for this error.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148462787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Mouse Ladder-Climb Protocol Induces Acute Anabolic Signaling and Muscle-Specific Adaptations to Resistance Training","authors":"Mayalen Valero-Breton,&nbsp;Marianny Portal-Rodriguez,&nbsp;Franco Tacchi,&nbsp;Javier Salgado-Valdovinos,&nbsp;María Cristina Miranda-Pilar,&nbsp;Eduardo Cifuentes-Silva,&nbsp;María Ignacia Martínez-Pérez,&nbsp;Marco Godoy,&nbsp;Josefa Bonicioli,&nbsp;Hugo Olguin,&nbsp;Luis Peñailillo,&nbsp;Jorge A. Soto,&nbsp;Claudio Cabello-Verrugio","doi":"10.1111/apha.70274","DOIUrl":"10.1111/apha.70274","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Resistance training has been shown to activate the protein synthesis pathway, leading to muscle growth in humans. However, this type of exercise has shown equivocal results in animal studies due to the difficulty of mimicking muscle overload in vivo. This study aimed to determine whether ladder-based exercise in mice induces canonical molecular, cellular, and functional adaptations to training.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mice performed a single exercise session or 6 weeks of training in the ladder climb. Acute responses included mTOR phosphorylation, puromycin incorporation, and mRNA levels of myogenic regulatory factors (MRF). Chronic adaptations were assessed by strength, fat-free mass, physical performance, and blood lactate levels to confirm the training load. Sarcomeric proteins were analyzed using Western blot, while histology measured muscle fiber diameter and satellite cell (SC) fusion. The SC amount was quantified by flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After a single exercise bout, mTOR phosphorylation increased at one and 3 h, with puromycin incorporation and MRF mRNA levels elevated at 8 h. After 6 weeks of training, the mice showed increased skeletal muscle strength and fat-free mass, with no changes in physical performance. Muscle-specific adaptations included increases in sarcomeric proteins and fiber diameters. SC adaptations were associated with an increased pool and enhanced capacity to fuse with muscle fibers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results demonstrate that ladder-based resistance exercise in mice induces molecular, cellular, and functional responses that are directionally consistent with adaptations reported after human resistance training, supporting its value for investigating the molecular and cellular mechanisms underlying this training.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression Landscape and Circadian Regulation of lncRNAs in the Kidney","authors":"Leonore Wigger,&nbsp;Fanny Durussel,&nbsp;Muriel Auberson,&nbsp;Dmitri Firsov,&nbsp;Yohan Bignon","doi":"10.1111/apha.70273","DOIUrl":"10.1111/apha.70273","url":null,"abstract":"<p>Recent multi-omics work shows that the diurnal rhythmicity of kidney function is associated with circadian oscillations in renal mRNA, protein and metabolite abundances. Yet circadian regulation of renal lncRNAs, which are emerging as important modulators of diverse (patho)physiological processes, remains largely unexplored. Here, we provide a comprehensive characterization of renal lncRNA expression across cell types and circadian time points using bulk RNA-Seq and single-nucleus RNA-Seq (snRNA-seq) using kidney samples from male mice. Although the majority of lncRNAs are lowly expressed and only a fraction are annotated, their profiles sufficed to distinguish nearly all renal cell types. Compared with mRNAs, lncRNAs were more cell-type specific and an inverse correlation between cell-type specificity and expression level was evident. To assess the role of the circadian clock, we used mice lacking the core-clock regulator BMAL1 in renal tubules. Approximately one-sixth of lncRNAs and one-third of mRNAs were rhythmic. In contrast with mRNAs, lncRNAs exhibited an asymmetric temporal distribution between night and day, with peak expression occurring preferentially during the inactive phase of the mice. <i>Bmal1</i> deletion partially disrupted rhythmicity in both biotypes and altered overall expression levels; lncRNAs were predominantly upregulated. These findings uncover the diversity of renal lncRNAs, their cellular distribution and their circadian regulation in male mice.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 8","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}