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Respiratory Research Aug 2017Airway remodelling is an important feature of asthma pathogenesis. A key structural change inherent in airway remodelling is increased airway smooth muscle mass. There... (Review)
Review
Airway remodelling is an important feature of asthma pathogenesis. A key structural change inherent in airway remodelling is increased airway smooth muscle mass. There is emerging evidence to suggest that the migration of airway smooth muscle cells may contribute to cellular hyperplasia, and thus increased airway smooth muscle mass. The precise source of these cells remains unknown. Increased airway smooth muscle mass may be collectively due to airway infiltration of myofibroblasts, neighbouring airway smooth muscle cells in the bundle, or circulating hemopoietic progenitor cells. However, the relative contribution of each cell type is not well understood. In addition, although many studies have identified pro and anti-migratory agents of airway smooth muscle cells, whether these agents can impact airway remodelling in the context of human asthma, remains to be elucidated. As such, further research is required to determine the exact mechanism behind airway smooth muscle cell migration within the airways, how much this contributes to airway smooth muscle mass in asthma, and whether attenuating this migration may provide a therapeutic avenue for asthma. In this review article, we will discuss the current evidence with respect to the regulation of airway smooth muscle cell migration in asthma.
Topics: Airway Remodeling; Asthma; Cell Movement; Humans; Muscle, Smooth; Myocytes, Smooth Muscle
PubMed: 28814293
DOI: 10.1186/s12931-017-0640-8 -
Cells Dec 2023Synaptopodin-2 (SYNPO2) is a protein associated with the Z-disc in striated muscle cells. It interacts with α-actinin and filamin C, playing a role in Z-disc...
Synaptopodin-2 (SYNPO2) is a protein associated with the Z-disc in striated muscle cells. It interacts with α-actinin and filamin C, playing a role in Z-disc maintenance under stress by chaperone-assisted selective autophagy (CASA). In smooth muscle cells, SYNPO2 is a component of dense bodies. Furthermore, it has been proposed to play a role in tumor cell proliferation and metastasis in many different kinds of cancers. Alternative transcription start sites and alternative splicing predict the expression of six putative SYNPO2 isoforms differing by extended amino- and/or carboxy-termini. Our analyses at mRNA and protein levels revealed differential expression of SYNPO2 isoforms in cardiac, skeletal and smooth muscle cells. We identified synemin, an intermediate filament protein, as a novel binding partner of the PDZ-domain in the amino-terminal extension of the isoforms mainly expressed in cardiac and smooth muscle cells, and demonstrated colocalization of SYNPO2 and synemin in both cell types. A carboxy-terminal extension, mainly expressed in smooth muscle cells, is sufficient for association with dense bodies and interacts with α-actinin. SYNPO2 therefore represents an additional and novel link between intermediate filaments and the Z-discs in cardiomyocytes and dense bodies in smooth muscle cells, respectively. In pathological skeletal muscle samples, we identified SYNPO2 in the central and intermediate zones of target fibers of patients with neurogenic muscular atrophy, and in nemaline bodies. Our findings help to understand distinct functions of individual SYNPO2 isoforms in different muscle tissues, but also in tumor pathology.
Topics: Humans; Actinin; Myocytes, Cardiac; Myocytes, Smooth Muscle; Protein Isoforms; Sarcomeres
PubMed: 38201288
DOI: 10.3390/cells13010085 -
Communications Biology Sep 2022Dystrophin is the central protein of the dystrophin-glycoprotein complex (DGC) in skeletal and heart muscle cells. Dystrophin connects the actin cytoskeleton to the... (Review)
Review
Dystrophin is the central protein of the dystrophin-glycoprotein complex (DGC) in skeletal and heart muscle cells. Dystrophin connects the actin cytoskeleton to the extracellular matrix (ECM). Severing the link between the ECM and the intracellular cytoskeleton has a devastating impact on the homeostasis of skeletal muscle cells, leading to a range of muscular dystrophies. In addition, the loss of a functional DGC leads to progressive dilated cardiomyopathy and premature death. Dystrophin functions as a molecular spring and the DGC plays a critical role in maintaining the integrity of the sarcolemma. Additionally, evidence is accumulating, linking the DGC to mechanosignalling, albeit this role is still less understood. This review article aims at providing an up-to-date perspective on the DGC and its role in mechanotransduction. We first discuss the intricate relationship between muscle cell mechanics and function, before examining the recent research for a role of the dystrophin glycoprotein complex in mechanotransduction and maintaining the biomechanical integrity of muscle cells. Finally, we review the current literature to map out how DGC signalling intersects with mechanical signalling pathways to highlight potential future points of intervention, especially with a focus on cardiomyopathies.
Topics: Dystrophin; Glycoproteins; Mechanotransduction, Cellular; Muscle Fibers, Skeletal; Sarcolemma
PubMed: 36168044
DOI: 10.1038/s42003-022-03980-y -
Respiratory Research Apr 2017Smooth muscle cell migration has been implicated in the development of respiratory and cardiovascular systems; and airway/vascular remodeling. Cell migration is a... (Review)
Review
Smooth muscle cell migration has been implicated in the development of respiratory and cardiovascular systems; and airway/vascular remodeling. Cell migration is a polarized cellular process involving a protrusive cell front and a retracting trailing rear. There are three cytoskeletal systems in mammalian cells: the actin cytoskeleton, the intermediate filament network, and microtubules; all of which regulate all or part of the migrated process. The dynamic actin cytoskeleton spatially and temporally regulates protrusion, adhesions, contraction, and retraction from the cell front to the rear. c-Abl tyrosine kinase plays a critical role in regulating actin dynamics and migration of airway smooth muscle cells and nonmuscle cells. Recent studies suggest that intermediate filaments undergo reorganization during migration, which coordinates focal adhesion dynamics, cell contraction, and nucleus rigidity. In particular, vimentin intermediate filaments undergo phosphorylation and reorientation in smooth muscle cells, which may regulate cell contraction and focal adhesion assembly/disassembly. Motile cells are characterized by a front-rear polarization of the microtubule framework, which regulates all essential processes leading to cell migration through its role in cell mechanics, intracellular trafficking, and signaling. This review recapitulates our current knowledge how the three cytoskeletal systems spatially and temporally modulate the migratory properties of cells. We also summarize the potential role of migration-associated biomolecules in lung and vascular diseases.
Topics: Actin Cytoskeleton; Animals; Cell Movement; Cells, Cultured; Cytoskeleton; Humans; Microtubules; Models, Biological; Myocytes, Smooth Muscle
PubMed: 28390425
DOI: 10.1186/s12931-017-0544-7 -
Vascular Pharmacology Oct 2023Vascular endothelial and smooth muscle cell dysfunction proceed the development of numerous vascular diseases, such as atherosclerosis. Both estrogen and progesterone... (Review)
Review
Vascular endothelial and smooth muscle cell dysfunction proceed the development of numerous vascular diseases, such as atherosclerosis. Both estrogen and progesterone receptors are present on vascular endothelial and smooth muscle cells, and therefore it has been postulated that these compounds may affect vascular function. It has been well-established that estrogen is a vasoprotective compound, however, the effects of progesterone on vascular function are not well understood. This narrative review summarizes the current research investigating the impact of both endogenous progesterone, and exogenous synthetic progestin on vascular endothelial and smooth muscle cell function and identifies discrepancies on their effects in vitro and in vivo. We speculate that an inverted-U dose response curve may exist between nitric oxide bioavailability and progesterone concentration, and that the androgenic properties of a progestin may influence vascular function. Future research is needed to discern the effects of both endogenous progesterone and exogenous progestin on vascular endothelial and smooth muscle cell function with consideration for the impacts of progesterone/progestin dose, and progestin type.
Topics: Humans; Progestins; Progesterone; Progesterone Congeners; Estrogens; Endothelial Cells; Atherosclerosis; Myocytes, Smooth Muscle
PubMed: 37591444
DOI: 10.1016/j.vph.2023.107209 -
Methods in Molecular Biology (Clifton,... 2018Ion channels are membrane proteins involved in almost all physiological processes, including neurotransmission, muscle contraction, pace-making activity, secretion,... (Review)
Review
Ion channels are membrane proteins involved in almost all physiological processes, including neurotransmission, muscle contraction, pace-making activity, secretion, electrolyte and water balance, immune response, and cell proliferation. Due to their broad distribution in human body and physiological roles, ion channels are attractive targets for drug discovery and safety pharmacology. Over the years ion channels have been associated to many genetic diseases ("channelopathies"). For most of these diseases the therapy is mainly empirical and symptomatic, often limited by lack of efficacy and tolerability for a number of patients. The search for the development of new and more specific therapeutic approaches is therefore strongly pursued. At the same time acquired channelopathies or dangerous side effects (such as proarrhythmic risk) can develop as a consequence of drugs unexpectedly targeting ion channels. Several noncardiovascular drugs are known to block cardiac ion channels, leading to potentially fatal delayed ventricular repolarization. Thus, the search of reliable preclinical cardiac safety testing in early stage of drug discovery is mandatory. To fulfill these needs, both ion channels drug discovery and toxicology strategies are evolving toward comprehensive research approaches integrating ad hoc designed in silico predictions and experimental studies for a more reliable and quick translation of results to the clinic side.Here we discuss two examples of how the combination of in silico methods and patch clamp experiments can help addressing drug discovery and safety issues regarding ion channels.
Topics: Animals; Cardiotoxicity; Databases, Chemical; Drug Discovery; Drug Evaluation, Preclinical; Humans; Ion Channels; Ligands; Models, Molecular; Muscle Cells; Patch-Clamp Techniques; Pharmacovigilance; Quantitative Structure-Activity Relationship; Stem Cells; Toxicology
PubMed: 29934900
DOI: 10.1007/978-1-4939-7899-1_15 -
Journal of Cellular Physiology Nov 2014Grb10 is an intracellular adaptor protein which binds directly to several growth factor receptors, including those for insulin and insulin-like growth factor receptor-1...
Grb10 is an intracellular adaptor protein which binds directly to several growth factor receptors, including those for insulin and insulin-like growth factor receptor-1 (IGF-1), and negatively regulates their actions. Grb10-ablated (Grb10(-/-) ) mice exhibit improved whole body glucose homeostasis and an increase in muscle mass associated specifically with an increase in myofiber number. This suggests that Grb10 may act as a negative regulator of myogenesis. In this study, we investigated in vitro, the molecular mechanisms underlying the increase in muscle mass and the improved glucose metabolism. Primary muscle cells isolated from Grb10(-/-) mice exhibited increased rates of proliferation and differentiation compared to primary cells isolated from wild-type mice. The improved proliferation capacity was associated with an enhanced phosphorylation of Akt and ERK in the basal state and changes in the expression of key cell cycle progression markers involved in regulating transition of cells from the G1 to S phase (e.g., retinoblastoma (Rb) and p21). The absence of Grb10 also promoted a faster transition to a myogenin positive, differentiated state. Glucose uptake was higher in Grb10(-/-) primary myotubes in the basal state and was associated with enhanced insulin signaling and an increase in GLUT4 translocation to the plasma membrane. These data demonstrate an important role for Grb10 as a link between muscle growth and metabolism with therapeutic implications for diseases, such as muscle wasting and type 2 diabetes.
Topics: Animals; Biomarkers; CD56 Antigen; Cell Cycle; Cell Differentiation; Cell Membrane; Cell Proliferation; Cell Separation; Cells, Cultured; Extracellular Signal-Regulated MAP Kinases; GRB10 Adaptor Protein; Gene Deletion; Gene Expression Regulation; Glucose; Insulin; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Muscle Cells; Muscle Fibers, Skeletal; Myoblasts, Skeletal; Myogenin; Protein Transport; Proto-Oncogene Proteins c-akt; RNA, Messenger; Satellite Cells, Skeletal Muscle
PubMed: 24664951
DOI: 10.1002/jcp.24628 -
Methods in Molecular Biology (Clifton,... 2017Microscopy in combination with contrast-increasing dyes allows the visualization and analysis of organs, tissues, and various cells. Because of their better resolution,...
Microscopy in combination with contrast-increasing dyes allows the visualization and analysis of organs, tissues, and various cells. Because of their better resolution, the development of confocal and laser microscopes enables the investigations of cell components, which are labeled with fluorescent dyes. The imaging of living cells on subcellular level (also in vivo) needs a labeling by gene transfection of GFP or similar labeled proteins. We present a method for visualization of cell structure in skeletal and heart muscle by label-free Second Harmonic Generation (SHG) microscopy and describe analytic methods for quantitative measurements of morphology and dynamics in skeletal muscle fibers.
Topics: Animals; Fluorescent Dyes; Green Fluorescent Proteins; Imaging, Three-Dimensional; Microscopy, Confocal; Muscle Fibers, Skeletal; Myocytes, Cardiac; Myosins; Photons; Sarcomeres; Second Harmonic Generation Microscopy
PubMed: 28470530
DOI: 10.1007/978-1-4939-6960-9_18 -
European Journal of Cell Biology Oct 2014Podosomes are adhesive, matrix remodeling organelles that have been described in numerous cell types, including all three vertebrate muscle cell lineages. Podosomes have... (Review)
Review
Podosomes are adhesive, matrix remodeling organelles that have been described in numerous cell types, including all three vertebrate muscle cell lineages. Podosomes have been intensively studied in smooth muscle cells, but they have also been described in cardiac myocytes and skeletal muscle cells where they are proposed to play a role in developmental remodeling of neuromuscular junction postsynaptic machinery. In this review, we summarize the current state of knowledge of podosomes in muscle cells, with a focus on their potential function at the maturing synapse.
Topics: Animals; Cell Fusion; Cell Surface Extensions; Humans; Muscle Fibers, Skeletal; Myocytes, Cardiac; Myocytes, Smooth Muscle; Neuromuscular Junction
PubMed: 25012928
DOI: 10.1016/j.ejcb.2014.06.002 -
Biotechnology and Bioengineering Jun 2019The paper presents a transient, continuum, two-phase model of the tissue engineering in fibrous scaffolds, including transport equations for the flowing culture medium,...
The paper presents a transient, continuum, two-phase model of the tissue engineering in fibrous scaffolds, including transport equations for the flowing culture medium, nutrient and cell concentration with transverse and in-plane diffusion and cell migration, a novel feature of local in-plane transport across a phenomenological pore and innovative layer-by-layer cell filling approach. The model is successfully validated for the smooth muscle cell tissue engineering of a vascular graft using crosslinked, electrospun gelatin fiber scaffolds for both static and dynamic cell culture, the latter in a dynamic bioreactor with a rotating shaft on which the tubular scaffold is attached. Parametric studies evaluate the impact of the scaffold microstructure, cell dynamics, oxygen transport, and static or dynamic conditions on the rate and extent of cell proliferation and depth of oxygen accessibility. An optimized scaffold of 75% dry porosity is proposed that can be tissue engineered into a viable and still fully oxygenated graft of the tunica media of the coronary artery within 2 days in the dynamic bioreactor. Such scaffold also matches the mechanical properties of the tunica media of the human coronary artery and the suture retention strength of a saphenous vein, often used as a coronary artery graft.
Topics: Blood Vessel Prosthesis; Computer Simulation; Coronary Vessels; Gelatin; Humans; Models, Biological; Myocytes, Smooth Muscle; Oxygen; Perfusion; Porosity; Tissue Engineering; Tissue Scaffolds
PubMed: 30737955
DOI: 10.1002/bit.26955