Journal of Muscle Research and Cell Motility最新文献

{"title":"Smooth muscle of the lower urinary tract: BK-RyR coupling in physiology and pathophysiology.","authors":"Monica Ridlon, Julia Tlapa, Kimberly Keil Stietz","doi":"10.1007/s10974-025-09707-w","DOIUrl":"https://doi.org/10.1007/s10974-025-09707-w","url":null,"abstract":"<p><p>In the lower urinary tract, coordinated function between the bladder and urethra is essential for normal micturition, requiring smooth muscle contraction and relaxation in a tightly regulated cycle. During the bladder filling phase, the bladder remains relaxed while the urethra stays contracted to prevent leakage. During voiding, this coordination reverses, and the bladder contracts to expel urine while the relaxed urethra allows urine flow. These functions are essential for proper micturition and two key molecular regulators of this process are the large-conductance calcium activated potassium (BK) channels and ryanodine receptors (RyRs), both of which modulate smooth muscle excitability and calcium dynamics. This review provides an overview of the roles of BK channels and RyR mediated signaling in regulating smooth muscle activity in the bladder and urethra, with a focus on their contributions to lower urinary tract physiology and pathophysiology. BK channels act as negative feedback modulators, dampening myogenic and nerve-evoked contractions of the detrusor and urethra. RyRs play a role in regulating intracellular calcium signaling that supports both muscle relaxation and contraction. This review highlights alterations in the function of these channels in lower urinary tract dysfunction, and as potential targets for other factors such as environmental exposures to disrupt voiding function. BK channels and RyRs are plausible targets for therapeutic strategies aimed at improving bladder and urethra function in certain patients, particularly those with lower urinary tract symptoms caused by factors such as aging and environmental chemical exposure.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-seq and ChIP-seq unveils thyroid hormone receptor α deficiency affects skeletal muscle myoblast proliferation and differentiation via Col6a1 during aging.","authors":"Runqing Shi, Gong Chen, Yusheng Zhang, Jiru Zhang, Lu Yan, Yu Duan","doi":"10.1007/s10974-025-09694-y","DOIUrl":"10.1007/s10974-025-09694-y","url":null,"abstract":"<p><p>Primary sarcopenia, an age-related syndrome, is a serious threat to the health and longevity of the elderly. Our prior studies indicated that thyroid hormone (TH) activity within muscle tissue undergoes significant age-associated alterations, mainly evidenced by a reduction in thyroid hormone receptor α (TRα) expression over time. TRα regulates the transcription of downstream target genes to exert its biological effects. Although TH is essential for skeletal muscle growth and development, the specific regulatory mechanism and broader role of TH binding its receptors in skeletal muscle aging remain unclear. We used ChIP-seq and RNA-seq to explore the aging changes of TRα target genes in gastrocnemius muscle of natural aging mouse model. ChIP-seq analysis revealed that TRα target genes are involved in nutrient synthesis, energy production, hormone secretion, and ECM-related pathways, suggesting a potential role of TRα in muscle growth, metabolism and component regulation. Further integration of RNA-seq showed that a greater number of down-regulated TRα target genes are associated with skeletal muscle aging. Through GSEA analysis and RT-qPCR screening, Col6a1 was identified as a key target gene. Col6a1 encodes collagen VI which is an important component of the ECM, ECM disorders and abnormal expression of Col6a1 can affect cell proliferation and differentiation. We confirmed that knockdown of Col6a1 inhibited the proliferation and differentiation of C2C12 cells. ChIP-qPCR and TRα silencing in C2C12 cells showed that TRα positively regulates Col6a1 transcription, and TRα deficiency inhibits the proliferation and differentiation of myoblasts, which is probably associated with Col6a1. These findings provide new insights into the molecular mechanisms underlying skeletal muscle aging and the regulatory roles of TH-TRα interactions.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":" ","pages":"167-182"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of neuromuscular transmission and Na⁺ channel inhibitors on strength-duration relationship in isolated slow- and fast-twitch muscles.","authors":"Mari S Matsumoto, Taku Hamada, Daiki Watanabe","doi":"10.1007/s10974-025-09702-1","DOIUrl":"10.1007/s10974-025-09702-1","url":null,"abstract":"<p><p>Strength-duration (S-D) relationship reflects muscle excitability which partially determines force production. Isolated muscle contains part of nerve and neuromuscular junction, suggesting that muscle excitation initiates not only muscle membrane but also nerve terminals and hence neuromuscular transmission (NMT). This study aimed to examine the effects of inhibition of neuromuscular transmission on S-D relationship in slow- and fast-twitch muscles of mice. Isolated slow-twitch soleus (SOL) and fast-twitch extensor digitorum longus (EDL) muscles were electrically stimulated, and minimal field strength required for force generation [threshold field strength (Th_FS)] was determined at various duration. Th_FS significantly increased in the presence of NMT inhibitors including pancuronium (Pan) and succinylcholine in both SOL and EDL muscles. Moreover, Th_FS in the presence of NMT inhibitors was higher in SOL compared to EDL. To clarify the mechanism of the different Th_FS between SOL and EDL, contribution of Na⁺ channel was investigated. In the presence of 1 μM Pan, partial inhibition of Na⁺ channel by tetrodotoxin eliminated the difference in Th_FS between EDL and SOL. These results suggest that (1) NMT significantly enhances muscle excitability, (2) threshold of action potential in fast-twitch muscle is greater compared with slow-twitch muscle if no existence of NMT, and (3) Na⁺ channel likely contribute to the difference between slow- and fast-twitch muscles.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":" ","pages":"231-238"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myoblast and fibroblast derived small extracellular vesicles differentially affect myoblast migration dynamics.","authors":"Kyle N Hagemann, Rhys S McColl, Jason A C Lovett, Celia Snyman, Kathryn H Myburgh","doi":"10.1007/s10974-025-09705-y","DOIUrl":"https://doi.org/10.1007/s10974-025-09705-y","url":null,"abstract":"<p><p>Muscle injury activates satellite cells and fibroblasts, with extracellular vesicles (EVs) mediating the related intercellular communication. The influence of EVs released by either cell type on recipient cell behaviour is still unclear. This study investigated the uptake and effects of EVs derived from C2C12 myoblasts (myo-EVs) and L929 fibroblasts (fibro-EVs) on proliferating myoblasts. Both cell lines were cultured in media largely depleted of FBS-derived EVs. Myo-EVs and fibro-EVs isolated from conditioned media were characterised using conventional methods. Effects of these EVs on myoblast function were assessed via PKH67-labelled EV uptake, proliferation, scratch closure, leading front migration rate and individual cell trajectories and western blot analysis for MyoD and Myogenin. Myoblasts preferentially internalised myo-EVs at 5 h (myo-EVs: 3.41 ± 1.34 vs fibro-EVs: 1.25 ± 1.13 puncta per cell) and 48 h (myo-EVs 16.55 ± 12.60 vs fibro-EVs 9.67 ± 4.88) (both p < 0.05). Under proliferative EV-depleted conditions, added EVs did not change myoblast proliferation. However, the elevated expression of Myogenin indicating a subtle shift toward differentiation. Myo-EVs increased myoblast migration rate into a scratch, compared to controls (13.77 ± 1.7 vs 11.08 ± 2.23 µm/h, p < 0.01), but had no effect under conditions of FBS EV depletion. On the other hand, fibro-EVs increased the speed of individual cells, but negatively affected leading front migration due to impaired myoblast persistence. These findings highlight the importance of cell-specific EV-mediated communication in muscle regeneration. Further, tissue explants used to generate cell-specific EVs for treatment should be free of contaminating cell types.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smooth muscle cells from skin perforator vessels as a new tool for vascular research.","authors":"Alisah Hussain, Yaw Asare-Amankwah, Nikolaos S Lymperopoulos, M Julie Thornton, Kirsten Riches-Suman","doi":"10.1007/s10974-025-09704-z","DOIUrl":"https://doi.org/10.1007/s10974-025-09704-z","url":null,"abstract":"<p><p>Vascular smooth muscle cells (SMC) comprise the medial layer of blood vessels and are responsible for maintaining vascular tone. Ordinarily quiescent and contractile, SMC can dedifferentiate into different phenotypes following injury or in disease states such as atherosclerosis and are thus valuable research tools for examining these conditions. The isolation of commonly used SMC types, such as those from the aorta or saphenous vein (SV), require clinical links or commercial supply and are rarely pathology-free. The skin is highly vascularised with perforator (Perf) vessels that protrude through the skin layers to feed the tissue. Whilst these vessels can be sourced from clinical procedures (e.g. reconstructive surgery), they are also available from elective cosmetic procedures such as abdominoplasty which could provide blood vessels unaffected by an underlying pathology. This paper describes the isolation of Perf-SMC for the first time, using a cost-effective explant technique. Explanted cells were confirmed as SMC by co-staining for alpha smooth muscle actin and smooth muscle myosin heavy chain. Phenotypic characteristics of Perf-SMC (cell morphology, proliferation, and multinucleation) were comparable to those from commonly used SMC from alternative vascular sources (SV-SMC and umbilical artery SMC). Furthermore, Perf-SMC were stable in culture up until at least passage 9 with no alteration in morphological characteristics or evidence of replication-induced phenotypic change. In summary, this paper describes an effective, efficient and low-cost method for isolating SMC from skin perforator vessels that may be a useful tool for the future examination of SMC behaviour from both pathological and healthy skin.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation and function of Pax3 in muscle stem cell heterogeneity and stress response.","authors":"Frederic Relaix, Virginia Zoglio, Sarah Chebouti, Joana Esteves de Lima, Peggy Lafuste","doi":"10.1007/s10974-025-09701-2","DOIUrl":"https://doi.org/10.1007/s10974-025-09701-2","url":null,"abstract":"","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal muscle: a biologists' adventure playground.","authors":"Terence Partridge","doi":"10.1007/s10974-025-09697-9","DOIUrl":"https://doi.org/10.1007/s10974-025-09697-9","url":null,"abstract":"<p><p>A brief discussion about skeletal muscle, aberrant expression of dystrophin from null mutations of the gene, potential explanations as to why this occurs, and how understanding this could be useful for potential therapies in the future.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The elementary step that generates force and sinusoidal analysis in striated muscle fibers.","authors":"Masataka Kawai","doi":"10.1007/s10974-025-09693-z","DOIUrl":"10.1007/s10974-025-09693-z","url":null,"abstract":"<p><p>The elementary step that generates force by cross-bridges (CBs) in striated muscles is reviewed. A literature search focused on models with validating data to verify a CB scheme; models without substantiating data were briefly mentioned or not included. Experimental data include those carried out under the isometric condition in muscle fibers and single myofibrils, along with results from single molecule and stopped-flow studies. These results suggest that force is generated before phosphate (Pi) is released, and the same force is maintained after Pi is released. These studies assumed that Pi is released from myosin. Some results from isotonic experiments are also reviewed, but the data lack the effect of Pi (or a weak effect). Studies with X-ray crystallography and cryo-electron microscopy suggested that force is generated after Pi release from the active site, and Pi is trapped at the secondary site before it is released to the solution. Thus, the difference in the definition of the \"Pi release step\" must have caused a controversy. It can be concluded that the results from physiological/single molecule studies and cryo-EM/crystal studies complement each other quite well. With isometric experiments, several perturbations are used to generate force transients: length change, chemical change, pressure release, and temperature increase. A small length change includes sinusoidal waveforms, and a large length change includes 10-20% release/restretch. Chemical perturbation includes [Pi] changes. With temperature studies it was shown that the force generation step is endothermic, indicating heat is absorbed. This is qualitatively explained by a hydrophobic interaction between actin and myosin, and by a cleft closure of myosin.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":" ","pages":"83-118"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasticity in leukocyte migration during haematopoiesis and inflammation.","authors":"C Villella, M Ciccioli, I M Anton, Y Calle","doi":"10.1007/s10974-025-09691-1","DOIUrl":"10.1007/s10974-025-09691-1","url":null,"abstract":"<p><p>Under normal physiological conditions, leukocytes and other tissue resident immune cells have been shown to migrate using the mesenchymal (integrin/adhesion dependent) and/or ameboid (integrin/adhesion independent) modes of migration. The objective of this manuscript is to provide a comprehensive literature review that illustrates how leukocytes display high levels of plasticity shifting between ameboid to mesenchymal modes of migration during haematopoiesis and the inflammatory response. This plasticity is shaped by the reciprocal regulation between the pattern of gene expression associated with their haematopoietic lineage or the leukocyte activation status, and the response to the physicochemical and topological characteristics of the surrounding tissue. The use of some common elements from the F-actin polymerising and actomyosin machinery in both modes of migration may facilitate the high capacity of leukocytes to alternate between the two migration modes while navigating a highly heterogenous landscape of physicochemical cues in their anatomical journey. We discuss this paradigm using detailed examples of specific leukocyte populations such as dendritic cells, macrophages and lymphocytes. We propose that cell adhesions involved in leukocyte migration represent signalling hubs where differentiation and physicochemical cues converge. These molecular complexes then generate signalling outputs that coordinate leukocyte expansion, differentiation, and optimal patterns of cell migration during haematopoiesis and leukocyte recruitment to inflammation sites.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":" ","pages":"135-151"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential impact of substrates on myosin heavy and light chain expression in human stem cell-derived cardiomyocytes at single-cell level.","authors":"Felix Osten, Alea K Bodenschatz, Karina Ivaskevica, Simon Kröhn, Birgit Piep, Tim Holler, Jana Teske, Judith Montag, Bogdan Iorga, Natalie Weber, Robert Zweigerdt, Theresia Kraft, Joachim D Meissner","doi":"10.1007/s10974-025-09690-2","DOIUrl":"10.1007/s10974-025-09690-2","url":null,"abstract":"<p><p>To fully exploit the potential of human pluripotent stem cell-derived cardiomyocytes, ideally they should acquire a mature, adult ventricular-like phenotype. Predominant expression of the β-isoform of myosin heavy chain (β-MyHC) and the ventricular isoform of myosin regulatory light chain 2 (MLC2v) is a marker of human adult cardiac ventricle. Yet predominant co-expression of these isoforms is rarely reported by current culture protocols. Here, we assessed the impact of different substrates on β-MyHC and MLC2v expression in single human embryonic stem cell-derived CMs (hESC-CMs). As substrates, surface materials with differing stiffness as defined by Young's modulus were combined with either laminin, a single-component coating, or Matrigel, a multi-component coating including growth factors. Semi-quantitative single-cell immunofluorescence analysis demonstrated that surfaces with supraphysiological stiffness in combination with laminin are sufficient for promotion of predominant β-MyHC expression, but not for predominant MLC2v expression in hESC-CMs. Accordingly, mechanical stimuli likely promote expression of β-MyHC in these cultures. Culture on matrices with a lower stiffness than glass in combination with growth factor-containing Matrigel led to only moderate increases in MLC2v expression, possibly more dependent on growth factors, suggesting different regulation of expression. Integrin-related downstream signal transducers, integrin-linked and cardiac troponin I-interacting kinase, as well as modulation of intracellular Ca²⁺-concentration and epigenetic signaling did not affect MyHC/MLC2 isoform expression. The data indicate that expression of adult ventricular markers β-MyHC and MLC2v depends on different stimuli like substrate stiffness and growth factors. To conclude, multiple stimuli appear to be necessary to promote an adult ventricular phenotype.</p>","PeriodicalId":16422,"journal":{"name":"Journal of Muscle Research and Cell Motility","volume":" ","pages":"119-133"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}