-
Current Opinion in Pharmacology Apr 2020Asthma is an obstructive inflammatory airway disease. Airway obstruction is mediated by hyperresponsive airway smooth muscle cell contraction, which is induced and... (Review)
Review
Asthma is an obstructive inflammatory airway disease. Airway obstruction is mediated by hyperresponsive airway smooth muscle cell contraction, which is induced and compounded by inflammation caused by T lymphocytes. One important signal transduction pathway that is involved in the activation of these cell types involves the generation of a lipid second messenger known as diacylglycerol (DAG). DAG levels are controlled in cells by a negative regulator known as DAG kinase (DGK). In this review, we discuss how the DAG signaling pathway attenuates the pathological function of immune cells and airway smooth muscle cells in allergic airway disease and asthma. Furthermore, we discuss how the enhancement of the DAG signaling pathway through the inhibition of DGK may represent a novel therapeutic strategy for these diseases.
Topics: Animals; Anti-Asthmatic Agents; Diacylglycerol Kinase; Humans; Hypersensitivity; Lung Diseases; Myocytes, Smooth Muscle; T-Lymphocytes
PubMed: 32836013
DOI: 10.1016/j.coph.2020.07.008 -
Current Protein & Peptide Science 2018There are two vertebrate talin genes, TLN1 and TLN2, which encode talin1 and talin2. Talin1 governs integrin activation, thus regulating focal adhesion (FA) assembly,... (Review)
Review
There are two vertebrate talin genes, TLN1 and TLN2, which encode talin1 and talin2. Talin1 governs integrin activation, thus regulating focal adhesion (FA) assembly, cell migration and invasion, but the biological function of talin2 remains to be elucidated and not too long ago talin2 was presumed to function redundantly with talin1. Recent studies have shown distinct differences between talin2 and talin1. The promoter of TLN2 is different from that of TLN1 in their size and binding to different transcription factors. Talin2 has a higher affinity to β -integrins than talin1. Talin2 regulates traction force generation, focal adhesion dynamics and invadopodium formation, thus controlling tumor cell migration, invasion and metastasis. Also, talin2 is enriched in the myotendinous junction (MTJ) in striated muscle, costameres and intercalated disks (ICDs) of cardiac myofibrils, and atherosclerotic plaques of blood vessels, thus regulating cardiovascular integrity. In this review, we discuss the differences between talin1 and talin2, in genome, protein expression pattern, affinity with integrins, traction force generation, and provide a glance at the roles of talin2 in cancer cell invasion and cardiovascular function.
Topics: Cardiovascular Diseases; Cardiovascular System; Cell Adhesion; Cell Differentiation; Cell Movement; Focal Adhesions; Humans; Integrins; Muscle Cells; Muscle, Skeletal; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Protein Conformation; Talin
PubMed: 30091412
DOI: 10.2174/1389203719666180809094731 -
Muscle & Nerve Oct 2016Duchenne muscular dystrophy (DMD) is caused by loss of the structural protein, dystrophin, resulting in muscle fragility. Muscle stem cell (MuSC) transplantation is a...
INTRODUCTION
Duchenne muscular dystrophy (DMD) is caused by loss of the structural protein, dystrophin, resulting in muscle fragility. Muscle stem cell (MuSC) transplantation is a potential therapy for DMD. It is unknown whether donor-derived muscle fibers are structurally innervated.
METHODS
Green fluorescent protein (GFP)-expressing MuSCs were transplanted into the tibials anterior of adult dystrophic mdx/mTR mice. Three weeks later the neuromuscular junction was labeled by immunohistochemistry.
RESULTS
The percent overlap between pre- and postsynaptic immunolabeling was greater in donor-derived GFP(+) myofibers, and fewer GFP(+) myofibers were identified as denervated compared with control GFP(-) fibers (P = 0.001 and 0.03). GFP(+) fibers also demonstrated acetylcholine receptor fragmentation and expanded endplate area, indicators of muscle reinnervation (P = 0.008 and 0.033).
CONCLUSION
It is unclear whether GFP(+) fibers are a result of de novo synthesis or fusion with damaged endogenous fibers. Either way, donor-derived fibers demonstrate clear histological innervation. Muscle Nerve 54: 763-768, 2016.
Topics: Animals; Mice; Mice, Inbred mdx; Mice, Transgenic; Muscle Cells; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Dystrophy, Animal; Muscular Dystrophy, Duchenne; Stem Cell Transplantation
PubMed: 26998682
DOI: 10.1002/mus.25115 -
Cells Apr 2022Many neuromuscular disease entities possess a significant disease burden and therapeutic options remain limited. Innovative human preclinical models may help to uncover... (Review)
Review
Many neuromuscular disease entities possess a significant disease burden and therapeutic options remain limited. Innovative human preclinical models may help to uncover relevant disease mechanisms and enhance the translation of therapeutic findings to strengthen neuromuscular disease precision medicine. By concentrating on idiopathic inflammatory muscle disorders, we summarize the recent evolution of the novel in vitro models to study disease mechanisms and therapeutic strategies. A particular focus is laid on the integration and simulation of multicellular interactions of muscle tissue in disease phenotypes in vitro. Finally, the requirements of a neuromuscular disease drug development workflow are discussed with a particular emphasis on cell sources, co-culture systems (including organoids), functionality, and throughput.
Topics: Coculture Techniques; Drug Development; Humans; Muscle Cells; Neuromuscular Diseases; Organoids
PubMed: 35406795
DOI: 10.3390/cells11071233 -
Environmental Science and Pollution... Mar 2021LncRNAs are one group of gene modulators functioning via several mechanisms in pathological and physiological conditions. We noted that LINC00472 expression level is...
LncRNAs are one group of gene modulators functioning via several mechanisms in pathological and physiological conditions. We noted that LINC00472 expression level is elevated in atherosclerotic coronary tissues compared with normal coronary artery samples. LINC00472 is also upregulated in vascular smooth muscle cells (VSMCs) induced by TNF-α and PDGF-BB. Ectopic expression of LINC00472 induced VSMC migration and proliferation. The predicted binding sequence between miR-149-3p and LINC00472 was analyzed by LncBase Predicted. Overexpression of miR-149-3p decreases the luciferase activity of wild-type reporter plasmid, but not the mutant one. Ectopic expression of LINC00472 suppresses the expression of miR-149-3p in VSMCs. Furthermore, we demonstrated that miR-149-3p expression is decreased in atherosclerotic coronary tissues. MiR-149-3p was downregulated in VSMCs induced by TNF-α and PDGF-BB. Overexpression of LINC00472 induces VSMC migration and proliferation via regulating miR-149-3p. These data suggested that LINC00472 acts a critical role in the migration and proliferation of VSMCs partly via modulating miR-149-3p.
Topics: Cell Movement; Cell Proliferation; MicroRNAs; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle
PubMed: 33095897
DOI: 10.1007/s11356-020-10761-9 -
Pediatric Cardiology Jan 2017Many different types of potassium channels with various functions exist in pulmonary artery smooth muscle cells, contributing to many physiological actions and... (Review)
Review
Many different types of potassium channels with various functions exist in pulmonary artery smooth muscle cells, contributing to many physiological actions and pathological conditions. The deep involvement of these channels in the onset and exacerbation of pulmonary arterial hypertension (PAH) also continues to be revealed. In 2013, KCNK3 (TASK1), which encodes a type of two-pore domain potassium channel, was shown to be a predisposing gene for PAH by genetic mutation, and it was added to the PAH classification at the Fifth World Symposium on Pulmonary Hypertension (Nice International Conference). Decreased expression and inhibited activity of voltage-gated potassium channels, particularly KCNA5 (Kv1.5), are also seen in PAH, regardless of the cause, and facilitation of pulmonary arterial contraction and vascular remodeling has been shown. The calcium-activated potassium channels seen in smooth muscle cells also change from BKca (Kca1.1) to IKca (Kca3.1) predominance in PAH due to transformation and have effects including the facilitation of smooth muscle cell migration, enhancement of proliferation, and inhibition of apoptosis. Elucidation of these roles for potassium channels in pulmonary vasoconstriction and remodeling may help bring new therapeutic strategies into view.
Topics: Animals; Humans; Hypertension, Pulmonary; Membrane Potentials; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Potassium Channels; Pulmonary Artery; Vascular Remodeling; Vasoconstriction
PubMed: 27826710
DOI: 10.1007/s00246-016-1491-7 -
Advances in Experimental Medicine and... 2021This chapter describes the current progress of basic research, and potential therapeutic applications primarily focused on the optical manipulation of muscle cells and...
This chapter describes the current progress of basic research, and potential therapeutic applications primarily focused on the optical manipulation of muscle cells and neural stem cells using microbial rhodopsin as a light-sensitive molecule. Since the contractions of skeletal, cardiac, and smooth muscle cells are mainly regulated through their membrane potential, several studies have been demonstrated to up- or downregulate the muscle contraction directly or indirectly using optogenetic actuators or silencers with defined stimulation patterns and intensities. Light-dependent oscillation of membrane potential also facilitates the maturation of myocytes with the development of T tubules and sarcomere structures, tandem arrays of minimum contractile units consists of contractile proteins and cytoskeletal proteins. Optogenetics has been applied to various stem cells and multipotent/pluripotent cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to generate light-sensitive neurons and to facilitate neuroscience. The chronic optical stimulation of the channelrhodopsin-expressing neural stem cells facilitates their neural differentiation. There are potential therapeutic applications of optogenetics in cardiac pacemaking, muscle regeneration/maintenance, locomotion recovery for the treatment of muscle paralysis due to motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Optogenetics would also facilitate maturation, network integration of grafted neurons, and improve the microenvironment around them when applied to stem cells.
Topics: Induced Pluripotent Stem Cells; Muscle Cells; Neural Stem Cells; Neurons; Optogenetics
PubMed: 33398826
DOI: 10.1007/978-981-15-8763-4_23 -
F1000Research 2018Almost 50 years ago, Earl Benditt and his son John described the clonality of the atherosclerotic plaque. This led Benditt to propose that the atherosclerotic lesion was... (Review)
Review
Almost 50 years ago, Earl Benditt and his son John described the clonality of the atherosclerotic plaque. This led Benditt to propose that the atherosclerotic lesion was a smooth muscle neoplasm, similar to the leiomyomata seen in the uterus of most women. Although the observation of clonality has been confirmed many times, interest in the idea that atherosclerosis might be a form of neoplasia waned because of the clinical success of treatments for hyperlipemia and because animal models have made great progress in understanding how lipid accumulates in the plaque and may lead to plaque rupture. Four advances have made it important to reconsider Benditt's observations. First, we now know that clonality is a property of normal tissue development. Second, this is even true in the vessel wall, where we now know that formation of clonal patches in that wall is part of the development of smooth muscle cells that make up the tunica media of arteries. Third, we know that the intima, the "soil" for development of the human atherosclerotic lesion, develops before the fatty lesions appear. Fourth, while the cells comprising this intima have been called "smooth muscle cells", we do not have a clear definition of cell type nor do we know if the initial accumulation is clonal. As a result, Benditt's hypothesis needs to be revisited in terms of changes in how we define smooth muscle cells and the quite distinct developmental origins of the cells that comprise the muscular coats of all arterial walls. Finally, since clonality of the lesions is real, the obvious questions are do these human tumors precede the development of atherosclerosis, how do the clones develop, what cell type gives rise to the clones, and in what ways do the clones provide the soil for development and natural history of atherosclerosis?
Topics: Animals; Clone Cells; Humans; Myocytes, Smooth Muscle; Plaque, Atherosclerotic; Tunica Intima; Tunica Media
PubMed: 30613386
DOI: 10.12688/f1000research.15994.1 -
Journal of Biomedical Materials... Nov 2022Human-induced pluripotent stem cells (hiPSC) and their differentiated vascular cells have been revolutionizing the field of regenerative wound healing. These cells are...
Human-induced pluripotent stem cells (hiPSC) and their differentiated vascular cells have been revolutionizing the field of regenerative wound healing. These cells are shown to be rejuvenated with immense potentials in secreting paracrine factors. Recently, hiPSC-derived vascular smooth muscle cells (hiPSC-VSMC) have shown regenerative wound healing ability via their paracrine secretion. The quest to modulate the secretory function of these hiPSC-VSMC is an ongoing effort and involves the use of both biochemical and biophysical stimuli. This study explores the development and optimization of a reproducible, inexpensive protocol to form hiPSC-VSMC derived spheroids to investigate the implications of spheroid size on viability and paracrine secretion. Our data show the successful formation of different sizes of spheroids using various amount of hiPSC-VSMC. The hiPSC-VSMC spheroids formed with 10,000 cells strike an ideal balance between overall cell health and maximal paracrine secretion. The conditioned medium from these spheroids was found to be bioactive in enhancing human dermal fibroblast cell proliferation and migration. This research will inform future studies on the optimal spheroid size for regenerative wound healing applications.
Topics: Cell Differentiation; Culture Media, Conditioned; Humans; Induced Pluripotent Stem Cells; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Spheroids, Cellular
PubMed: 35815599
DOI: 10.1002/jbm.a.37423 -
Journal of Basic and Clinical... Nov 2022Bioenergetics is the study of energy flow between biological systems and the surroundings and is measured quantitatively. Energy flow can be affected by many variables,... (Review)
Review
Bioenergetics is the study of energy flow between biological systems and the surroundings and is measured quantitatively. Energy flow can be affected by many variables, including lifestyle and exercise, where exercise comes in different types; endurance and resistance training play significant roles in enhancing bioenergetics and promoting health. In addition, a supplementary diet supports recovery and energy production. This review aims to study the effect of endurance training, resistance training, and supplement intake on the muscle cell's bioenergetics. As a conclusion of the information presented in this mini-review, it was found that resistance, endurance training, and supplements can increase mitochondrial biogenesis, fat oxidation, myofibril synthesis, and increase VO max.
Topics: Humans; Resistance Training; Physical Endurance; Muscle, Skeletal; Energy Metabolism; Mitochondria; Muscle Cells
PubMed: 34687594
DOI: 10.1515/jbcpp-2021-0261