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Cellular Signalling Jan 2019Excessive vascular smooth muscle cell (SMC) proliferation, migration and extracellular matrix (ECM) synthesis are key events in the development of intimal hyperplasia, a... (Review)
Review
Excessive vascular smooth muscle cell (SMC) proliferation, migration and extracellular matrix (ECM) synthesis are key events in the development of intimal hyperplasia, a pathophysiological response to acute or chronic sources of vascular damage that can lead to occlusive narrowing of the vessel lumen. Atherosclerosis, the primary cause of coronary artery disease, is characterised by chronic vascular inflammation and dyslipidemia, while revascularisation surgeries such as coronary stenting and bypass grafting represent acute forms of vascular injury. Gene knockouts of transforming growth factor-beta (TGFβ), its receptors and downstream signalling proteins have demonstrated the importance of this pleiotropic cytokine during vasculogenesis and in the maintenance of vascular homeostasis. Dysregulated TGFβ signalling is a hallmark of many vascular diseases, and has been associated with the induction of pathological vascular cell phenotypes, fibrosis and ECM remodelling. Here we present an overview of TGFβ signalling in SMCs, highlighting the ways in which this multifaceted cytokine regulates SMC behaviour and phenotype in cardiovascular diseases driven by intimal hyperplasia.
Topics: Animals; Cell Movement; Cell Proliferation; Coronary Artery Disease; Humans; Myocytes, Smooth Muscle; Signal Transduction; Transforming Growth Factor beta
PubMed: 30227237
DOI: 10.1016/j.cellsig.2018.09.004 -
Cells Mar 2021Muscle tissue is often removed during hamstring tendon graft preparation for anterior cruciate ligament (ACL) reconstruction. The purpose of the study was to test...
Muscle tissue is often removed during hamstring tendon graft preparation for anterior cruciate ligament (ACL) reconstruction. The purpose of the study was to test whether preservation of muscle remnants on a tendon graft is beneficial to the graft healing process following ACL reconstruction. Co-culturing of tendon-derived cells (TDCs) and muscle-derived cells (MDCs) was performed at various ratios, and their potential for cell viability and multilineage differentiation was compared to a single TDC cell group. Ligamentous and chondrogenic differentiation was most enhanced when a small population of MDCs was co-cultured with TDCs (6:2 co-culture group). Cell viability and osteogenic differentiation were proportionally enhanced with increasing MDC population size. MDCs co-cultured with TDCs possess both the ability to enhance cell viability and differentiate into other cell lineages.
Topics: Adolescent; Adult; Becaplermin; Calcification, Physiologic; Cell Differentiation; Cell Survival; Chondrocytes; Chondrogenesis; Coculture Techniques; Collagen; Extracellular Matrix; Female; Gene Expression Regulation; Hamstring Tendons; Humans; Ligaments; Male; Muscle Cells; Osteogenesis; Preservation, Biological; Young Adult
PubMed: 33801626
DOI: 10.3390/cells10040740 -
Skeletal Muscle Dec 2021Measuring biological features of skeletal muscle cells is difficult because of their unique morphology and multinucleate nature upon differentiation. Here, we developed...
BACKGROUND
Measuring biological features of skeletal muscle cells is difficult because of their unique morphology and multinucleate nature upon differentiation. Here, we developed a new Fiji macro package called ViaFuse (that stands for viability and fusion) to measure skeletal muscle cell viability and differentiation. To test ViaFuse, we utilized immunofluorescence images of differentiated myotubes where the capping actin protein of muscle z-line subunit beta (CAPZB) was depleted in comparison with control cells.
RESULTS
We compared the values achieved using the ViaFuse macros first with manual quantification performed by researchers and second with those obtained utilizing the MATLAB muscle-centric software MyoCount. We observed a high degree of correlation between all methods of quantification.
CONCLUSIONS
ViaFuse can detect the borders of myotubes and identify nuclear clumps which have been limitations of previous muscle-centric imaging software. The ViaFuse macros require little computer power or space to run and user inputs to the ViaFuse macros are minimal, thereby automating the analysis process in a quick, easy, and accurate fashion. Additionally, the ViaFuse macros work with Fiji, an existing imaging software widely used by skeletal muscle researchers. Furthermore, ViaFuse is compatible with many computer systems, has a very intuitive interface, and does not require prior complex mathematical knowledge. Therefore, we propose ViaFuse as a robust and meticulous method to quantify skeletal muscle cell viability and differentiation.
Topics: Cell Differentiation; Cell Survival; Fiji; Muscle Fibers, Skeletal; Muscle, Skeletal
PubMed: 34915930
DOI: 10.1186/s13395-021-00284-3 -
Redox Biology 2015Autophagy regulates the metabolism, survival, and function of numerous cell types, including those comprising the cardiovascular system. In the vasculature, changes in... (Review)
Review
Autophagy regulates the metabolism, survival, and function of numerous cell types, including those comprising the cardiovascular system. In the vasculature, changes in autophagy have been documented in atherosclerotic and restenotic lesions and in hypertensive vessels. The biology of vascular smooth muscle cells appears particularly sensitive to changes in the autophagic program. Recent evidence indicates that stimuli or stressors evoked during the course of vascular disease can regulate autophagic activity, resulting in modulation of VSMC phenotype and viability. In particular, certain growth factors and cytokines, oxygen tension, and pharmacological drugs have been shown to trigger autophagy in smooth muscle cells. Importantly, each of these stimuli has a redox component, typically associated with changes in the abundance of reactive oxygen, nitrogen, or lipid species. Collective findings support the hypothesis that autophagy plays a critical role in vascular remodeling by regulating smooth muscle cell phenotype transitions and by influencing the cellular response to stress. In this graphical review, we summarize current knowledge on the role of autophagy in the biology of the smooth muscle cell in (patho)physiology.
Topics: Atherosclerosis; Autophagy; Humans; Lipid Metabolism; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Oxidative Stress
PubMed: 25544597
DOI: 10.1016/j.redox.2014.12.007 -
Current Osteoporosis Reports Oct 2019Bone and muscle mass increase in response to mechanical loading and biochemical cues. Bone-forming osteoblasts differentiate into early osteocytes which ultimately... (Review)
Review
PURPOSE OF REVIEW
Bone and muscle mass increase in response to mechanical loading and biochemical cues. Bone-forming osteoblasts differentiate into early osteocytes which ultimately mature into late osteocytes encapsulated in stiff calcified matrix. Increased muscle mass originates from muscle stem cells (MuSCs) enclosed between their plasma membrane and basal lamina. Stem cell fate and function are strongly determined by physical and chemical properties of their microenvironment, i.e., the cell niche.
RECENT FINDINGS
The cellular niche is a three-dimensional structure consisting of extracellular matrix components, signaling molecules, and/or other cells. Via mechanical interaction with their niche, osteocytes and MuSCs are subjected to mechanical loads causing deformations of membrane, cytoskeleton, and/or nucleus, which elicit biochemical responses and secretion of signaling molecules into the niche. The latter may modulate metabolism, morphology, and mechanosensitivity of the secreting cells, or signal to neighboring cells and cells at a distance. Little is known about how mechanical loading of bone and muscle tissue affects osteocytes and MuSCs within their niches. This review provides an overview of physicochemical niche conditions of (early) osteocytes and MuSCs and how these are sensed and determine cell fate and function. Moreover, we discuss how state-of-the-art imaging techniques may enhance our understanding of these conditions and mechanisms.
Topics: Animals; Cell Differentiation; Extracellular Matrix; Humans; Mechanotransduction, Cellular; Muscle Cells; Osteocytes; Stress, Mechanical
PubMed: 31428977
DOI: 10.1007/s11914-019-00522-0 -
FASEB Journal : Official Publication of... Nov 2021Kabuki syndrome (KS) is a rare genetic disorder caused primarily by mutations in the histone modifier genes KMT2D and KDM6A. The genes have broad temporal and spatial...
Kabuki syndrome (KS) is a rare genetic disorder caused primarily by mutations in the histone modifier genes KMT2D and KDM6A. The genes have broad temporal and spatial expression in many organs, resulting in complex phenotypes observed in KS patients. Hypotonia is one of the clinical presentations associated with KS, yet detailed examination of skeletal muscle samples from KS patients has not been reported. We studied the consequences of loss of KMT2D function in both mouse and human muscles. In mice, heterozygous loss of Kmt2d resulted in reduced neuromuscular junction (NMJ) perimeter, decreased muscle cell differentiation in vitro and impaired myofiber regeneration in vivo. Muscle samples from KS patients of different ages showed presence of increased fibrotic tissue interspersed between myofiber fascicles, which was not seen in mouse muscles. Importantly, when Kmt2d-deficient muscle stem cells were transplanted in vivo in a physiologic non-Kabuki environment, their differentiation potential is restored to levels undistinguishable from control cells. Thus, the epigenetic changes due to loss of function of KMT2D appear reversible through a change in milieu, opening a potential therapeutic avenue.
Topics: Abnormalities, Multiple; Adolescent; Animals; Cell Differentiation; Child; Child, Preschool; DNA-Binding Proteins; Disease Models, Animal; Face; Female; Hematologic Diseases; Histone-Lysine N-Methyltransferase; Humans; Infant; Male; Mice; Mice, Transgenic; Muscle Cells; Muscle Fibers, Skeletal; Mutation; Myeloid-Lymphoid Leukemia Protein; Neoplasm Proteins; Neuromuscular Junction; Signal Transduction; Vestibular Diseases
PubMed: 34613626
DOI: 10.1096/fj.202100823R -
Current Molecular Medicine 2015Besides being involved in the gradual formation of blood vessels during embryonic development, vascular remodeling also contributes to the progression of various... (Review)
Review
Besides being involved in the gradual formation of blood vessels during embryonic development, vascular remodeling also contributes to the progression of various cardiovascular diseases, such as; myocardial infarction, heart failure, atherosclerosis, pulmonary artery hypertension, restenosis, aneurysm, etc. The integrated mechanisms; proliferation of medial smooth muscle cell, dysregulation of intimal endothelial cell, activation of adventitial fibroblast, inflammation of macrophage, and the participation of extracellular matrix proteins are important factors in vascular remodeling. In the recent studies, microRNAs (miRs) have been shown to be expressed in all of these cell-types and play important roles in the mechanisms of vascular remodeling. Therefore, some miRs may be involved in prevention and others in the aggravation of the vascular lesions. miRs are small, endogenous, conserved, single-stranded, non-coding RNAs; which degrade target RNAs or inhibit translation post-transcriptionally. In this paper, we reviewed the function and mechanisms of miRs, which are highly expressed in various cells types, especially endothelial and smooth muscle cells, which are closely involved in the process of vascular remodeling. We also assess the functions of these miRs in the hope that they may provide new possibilities of diagnosis and treatment choices for the related diseases.
Topics: Animals; Cardiovascular Diseases; Endothelial Cells; Gene Expression Regulation; Humans; Macrophages; MicroRNAs; Myocytes, Cardiac; Myocytes, Smooth Muscle; Neovascularization, Pathologic; Signal Transduction; Vascular Remodeling
PubMed: 26391551
DOI: 10.2174/1566524015666150921105031 -
Molecular Medicine Reports Jan 2021The reconstruction of pulmonary vascular structure caused by the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) is the central link in...
The reconstruction of pulmonary vascular structure caused by the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) is the central link in the formation of pulmonary arterial hypertension (PAH). Platelet‑derived growth factor (PDGF) can regulate the proliferation and migration of PASMCs. At the same time, nuclear factor of activated T cells (NFATs) plays an important role in the development of PAH. To the best of our knowledge, there are no reports yet regarding whether PDGF regulates NFATc2 to increase the proliferation of PASMCs. The present study aimed to investigate whether PDGF affects the proliferation and migration of PASMCs by regulating NFAT, and to study the pathogenesis of PAH. PASMCs were treated with recombinant PDGF; Cell Counting Kit‑8 and clone formation experiments showed that PDGF enhanced the cell viability and proliferation of PASMCs. Cell cycle distribution and molecular markers related to cell proliferation (cyclin D1, CDK4 and Proliferating Cell Nuclear Antigen) were detected by flow cytometry, and the results indicated that PDGF promoted the division of PAMSCs. The scratch migration and Transwell migration assays showed that the migratory ability of PASMCs was enhanced following PDGF treatment. Changes in NFATs (NFATc1‑5) after PDGF treatment were evaluated by reverse transcription‑quantitative PCR and western blotting; NFATc2 showed the most significant results. Finally, PDGF‑treated cells were treated with an NFAT pathway inhibitor, cyclosporin A, or a small interfering RNA targeting NFATc2, and changes in cell proliferation and migration were evaluated to assess the role of NFATc2 in PDGF‑induced cell proliferation and migration. In conclusion, PDGF may regulate PASMC proliferation and migration by regulating the expression of NFAT, further leading to the occurrence of PAH. It is proposed that NFATc2 could be used as a potential target for PAH treatment.
Topics: Animals; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Cyclosporine; Myocytes, Smooth Muscle; NFATC Transcription Factors; Platelet-Derived Growth Factor; Pulmonary Artery; RNA, Small Interfering; Rats
PubMed: 33179105
DOI: 10.3892/mmr.2020.11677 -
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 -
Journal of Muscle Research and Cell... Jun 2019Vascular smooth muscle cells (VSMCs) are the predominant cell type in the blood vessel wall and normally adopt a quiescent, contractile phenotype. VSMC migration is... (Review)
Review
Vascular smooth muscle cells (VSMCs) are the predominant cell type in the blood vessel wall and normally adopt a quiescent, contractile phenotype. VSMC migration is tightly controlled, however, disease associated changes in the soluble and insoluble environment promote VSMC migration. Classically, studies investigating VSMC migration have described the influence of soluble factors. Emerging data has highlighted the importance of insoluble factors, including extracellular matrix stiffness and porosity. In this review, we will recap on the important signalling pathways that regulate VSMC migration and reflect on the potential importance of emerging regulators of VSMC function.
Topics: Animals; Cell Movement; Extracellular Matrix; Humans; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle
PubMed: 31254136
DOI: 10.1007/s10974-019-09531-z