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Trends in Cardiovascular Medicine May 2009Vascular calcification, a prevalent and progressive disorder, involves numerous interactive, autocrine, paracrine, and endocrine regulatory mechanisms and is thus... (Review)
Review
Vascular calcification, a prevalent and progressive disorder, involves numerous interactive, autocrine, paracrine, and endocrine regulatory mechanisms and is thus ideally suited for analysis using a systems approach. This approach focuses on creating quantitative, testable models of complex biological systems that take into consideration the time dimension. They are usually expressed as mathematical models, and because of their time dependence and complexity, they usually require computer simulation to determine predicted outcomes. Here, we provide an example of such a model used to analyze self-organization and mineralization of vascular stem cells, using partial differential equations capable of accurately predicting experimental outcomes. Such systems-based models are useful in many aspects of cardiovascular medicine.
Topics: Calcinosis; Computer Simulation; Feedback, Physiological; Humans; Models, Cardiovascular; Signal Transduction; Stem Cells; Systems Biology; Vascular Diseases
PubMed: 19818947
DOI: 10.1016/j.tcm.2009.07.002 -
Journal of Biological Engineering 2019The ovarian follicle is the structural and functional unit of the ovary, composed of the female gamete (the oocyte) and supportive somatic cells. Follicles are not only... (Review)
Review
The ovarian follicle is the structural and functional unit of the ovary, composed of the female gamete (the oocyte) and supportive somatic cells. Follicles are not only the source of a female's germ cell supply, but also secrete important hormones necessary for proper endocrine function. Folliculogenesis, the growth and maturation of the follicular unit, is a complex process governed by both intrafollicular crosstalk and pituitary-secreted hormones. While the later stages of this process are gonadotropin-dependent, early folliculogenesis appears to be controlled by the ovarian microenvironment and intrafollicular paracrine and autocrine signaling. In vitro follicle culture remains challenging because of the limited knowledge of growth factors and other cytokines influencing early follicle growth. Here we discuss the current state of knowledge on paracrine and autocrine signaling influencing primary follicles as they develop into the antral stage. Given the importance of intrafollicular signaling and the ovarian microenvironment, we reviewed the current engineering approaches for in vitro follicle culture, including 3D systems using natural hydrogels such as alginate and synthetic hydrogels such as poly(ethylene glycol). Our discussion is focused on what drives the proliferation of granulosa cells, development of the thecal layer, and antrum formation-three processes integral to follicle growth up to the antral stage. Further research in this area may reveal the mechanisms behind these complex signaling relationships within the follicle, leading to more successful and physiologically-relevant in vitro culture methods that will translate well to clinical applications.
PubMed: 30647770
DOI: 10.1186/s13036-018-0134-3 -
Current Opinion in Systems Biology Dec 2019Communicating is crucial for cells to coordinate their behaviors. Immunological processes, involving diverse cytokines and cell types, are ideal for developing... (Review)
Review
Communicating is crucial for cells to coordinate their behaviors. Immunological processes, involving diverse cytokines and cell types, are ideal for developing frameworks for modeling coordinated behaviors of cells. Here, we review recent studies that combine modeling and experiments to reveal how immune systems use autocrine, paracrine, and juxtacrine signals to achieve behaviors such as controlling population densities and hair regenerations. We explain that models are useful because one can computationally vary numerous parameters, in experimentally infeasible ways, to evaluate alternate immunological responses. For each model, we focus on the length-scales and time-scales involved and explain why integrating multiple length-scales and time-scales in a model remain challenging. We suggest promising modeling strategies for meeting this challenge and their practical consequences.
PubMed: 31922054
DOI: 10.1016/j.coisb.2019.10.008 -
Current Hypertension Reports Sep 2017The rising prevalence of primary pediatric hypertension and its tracking into adult hypertension point to the importance of determining its pathogenesis to gain insights... (Review)
Review
The rising prevalence of primary pediatric hypertension and its tracking into adult hypertension point to the importance of determining its pathogenesis to gain insights into its current and emerging management. Considering that the intricate control of BP is governed by a myriad of anatomical, molecular biological, biochemical, and physiological systems, multiple genes are likely to influence an individual's BP and susceptibility to develop hypertension. The long-term regulation of BP rests on renal and non-renal mechanisms. One renal mechanism relates to sodium transport. The impaired renal sodium handling in primary hypertension and salt sensitivity may be caused by aberrant counter-regulatory natriuretic and anti-natriuretic pathways. The sympathetic nervous and renin-angiotensin-aldosterone systems are examples of antinatriuretic pathways. An important counter-regulatory natriuretic pathway is afforded by the renal autocrine/paracrine dopamine system, aberrations of which are involved in the pathogenesis of hypertension, including that associated with obesity. We present updates on the complex interactions of these two systems with dietary salt intake in relation to obesity, insulin resistance, inflammation, and oxidative stress. We review how insults during pregnancy such as maternal and paternal malnutrition, glucocorticoid exposure, infection, placental insufficiency, and treatments during the neonatal period have long-lasting effects in the regulation of renal function and BP. Moreover, these effects have sex differences. There is a need for early diagnosis, frequent monitoring, and timely management due to increasing evidence of premature target organ damage. Large controlled studies are needed to evaluate the long-term consequences of the treatment of elevated BP during childhood, especially to establish the validity of the current definition and treatment of pediatric hypertension.
Topics: Child; Early Medical Intervention; Humans; Hypertension; Insulin Resistance; Obesity; Oxidative Stress; Renin-Angiotensin System; Sodium Chloride, Dietary
PubMed: 28780627
DOI: 10.1007/s11906-017-0768-4 -
Clinical Science (London, England :... Sep 2012The RAS (renin-angiotensin system) is one of the earliest and most extensively studied hormonal systems. The RAS is an atypical hormonal system in several ways. The... (Review)
Review
The RAS (renin-angiotensin system) is one of the earliest and most extensively studied hormonal systems. The RAS is an atypical hormonal system in several ways. The major bioactive peptide of the system, AngII (angiotensin II), is neither synthesized in nor targets one specific organ. New research has identified additional peptides with important physiological and pathological roles. More peptides also mean newer enzymatic cascades that generate these peptides and more receptors that mediate their function. In addition, completely different roles of components that constitute the RAS have been uncovered, such as that for prorenin via the prorenin receptor. Complexity of the RAS is enhanced further by the presence of sub-systems in tissues, which act in an autocrine/paracrine manner independent of the endocrine system. The RAS seems relevant at the cellular level, wherein individual cells have a complete system, termed the intracellular RAS. Thus, from cells to tissues to the entire organism, the RAS exhibits continuity while maintaining independent control at different levels. The intracellular RAS is a relatively new concept for the RAS. The present review provides a synopsis of the literature on this system in different tissues.
Topics: Angiotensin II; Fibroblasts; Humans; Kidney; Muscle, Smooth, Vascular; Myocytes, Cardiac; Renin-Angiotensin System; Signal Transduction
PubMed: 22590974
DOI: 10.1042/CS20120089 -
Poultry Science Jul 1994Leukocytic cytokines are produced by cells of the immune system and are prominent regulators of the immune response and in some cases various systemic responses.... (Review)
Review
Leukocytic cytokines are produced by cells of the immune system and are prominent regulators of the immune response and in some cases various systemic responses. Leukocytic cytokines are released during immune responses and may act in autocrine, paracrine, or endocrine manners. Although over a dozen avian leukocytic cytokines have been described based on functional activities, characterization at the molecular level is not well developed. Two exceptions are 1) myelomonocytic growth factor, a colony-stimulating factor-like cytokine required for the growth and differentiation of hematopoietic precursor cells, particularly myelomonocytic cells; and 2) the avian transforming growth factor-beta (TGF-beta) family of cytokines, which modulate wound healing, bone metabolism, and cellular differentiation. Cytokines with bioactivities similar to mammalian interleukin (IL)-1, IL-2, IL-6, and interferon-gamma have been at least partially purified. Cytokines with bioactivities similar to mammalian IL-8, colony-stimulating factor, and tumor necrosis factor-alpha have been reported but are not well characterized at the molecular level. With a few exceptions, including TGF-beta and thymulin, highly purified leukocytic cytokines of mammalian origin have diminished or no specific activity in avian assay systems. The chicken IL-1 receptor has been cloned and the predicted amino acid sequence shares 60% homology with the human IL-1 receptor. A component of the chicken IL-2 receptor has been partially purified but little is known about other avian leukocytic cytokine receptors. Potential applications of leukocytic cytokines in poultry production originate from their regulation of a variety of functions such as disease resistance, would healing, bone accretion, nutrient partitioning, appetite, growth, and reproduction.
Topics: Animal Husbandry; Animals; Birds; Cytokines; Leukocytes; Mammals; Poultry; Receptors, Cytokine
PubMed: 7937464
DOI: 10.3382/ps.0731035 -
Frontiers in Immunology 2014Bidirectional interactions between the immune and the nervous systems are of considerable interest both for deciphering their functioning and for designing novel... (Review)
Review
Bidirectional interactions between the immune and the nervous systems are of considerable interest both for deciphering their functioning and for designing novel therapeutic strategies. The past decade has brought a burst of insights into the molecular mechanisms involved in neuroimmune communications mediated by dopamine. Studies of dendritic cells (DCs) revealed that they express the whole machinery to synthesize and store dopamine, which may act in an autocrine manner to stimulate dopamine receptors (DARs). Depending on specific DARs stimulated on DCs and T cells, dopamine may differentially favor CD4(+) T cell differentiation into Th1 or Th17 inflammatory cells. Regulatory T cells can also release high amounts of dopamine that acts in an autocrine DAR-mediated manner to inhibit their suppressive activity. These dopaminergic regulations could represent a driving force during autoimmunity. Indeed, dopamine levels are altered in the brain of mouse models of multiple sclerosis (MS) and lupus, and in inflamed tissues of patients with inflammatory bowel diseases or rheumatoid arthritis (RA). The distorted expression of DARs in peripheral lymphocytes of lupus and MS patients also supports the importance of dopaminergic regulations in autoimmunity. Moreover, dopamine analogs had beneficial therapeutic effects in animal models, and in patients with lupus or RA. We propose models that may underlie key roles of dopamine and its receptors in autoimmune diseases.
PubMed: 24711809
DOI: 10.3389/fimmu.2014.00117 -
Journal of Cellular and Molecular... Oct 2018Fever is a fundamental response to infection and a hallmark of inflammatory disease, which has been conserved and shaped through millions of years of natural selection.... (Review)
Review
Fever is a fundamental response to infection and a hallmark of inflammatory disease, which has been conserved and shaped through millions of years of natural selection. Although fever is able to stimulate both innate and adaptive immune responses, the very nature of all the molecular thermosensors, the timing and the detailed mechanisms translating a physical trigger into a fundamental biological response are incompletely understood. Here we discuss the consequence of hyperthermic stress in dendritic cells (DCs), and how the sole physical input is sensed as an alert stimulus triggering a complex transition in a very narrow temporal window. Importantly, we review recent findings demonstrating the significant and specific changes discovered in gene expression and in the metabolic phenotype associated with hyperthermia in DCs. Furthermore, we discuss the results that support a model based on a thermally induced autocrine signalling, which rewires and sets a metabolism checkpoint linked to immune activation of dendritic cells. Importantly, in this context, we highlight the novel regulatory functions discovered for IGFBP-6 protein: induction of chemotaxis; capacity to increase oxidative burst and degranulation of neutrophils, ability to induce metabolic changes in DCs. Finally, we discuss the role of IGFBP-6 in autoimmune disease and how novel mechanistic insights could lead to exploit thermal stress-related mechanisms in the context of cancer therapy.
Topics: Adaptive Immunity; Animals; Autocrine Communication; Autoimmune Diseases; Cell Degranulation; Chemotaxis; Dendritic Cells; Fever; Gene Expression Regulation; HSP70 Heat-Shock Proteins; Humans; Immunity, Innate; Inflammation; Insulin-Like Growth Factor Binding Protein 6; Neoplasms; Neutrophils; Receptor, IGF Type 2
PubMed: 30117676
DOI: 10.1111/jcmm.13738 -
European Journal of Biochemistry Jan 2004The hypothesis that l-glutamate (Glu) is an excitatory amino acid neurotransmitter in the mammalian central nervous system is now gaining more support after the... (Review)
Review
The hypothesis that l-glutamate (Glu) is an excitatory amino acid neurotransmitter in the mammalian central nervous system is now gaining more support after the successful cloning of a number of genes coding for the signaling machinery required for this neurocrine at synapses in the brain. These include Glu receptors (signal detection), Glu transporters (signal termination) and vesicular Glu transporters (signal output through exocytotic release). Relatively little attention has been paid to the functional expression of these molecules required for Glu signaling in peripheral neuronal and non-neuronal tissues; however, recent molecular biological analyses show a novel function for Glu as an extracellular signal mediator in the autocrine and/or paracrine system. Emerging evidence suggests that Glu could play a dual role in mechanisms underlying the maintenance of cellular homeostasis - as an excitatory neurotransmitter in the central neurocrine system and an extracellular signal mediator in peripheral autocrine and/or paracrine tissues. In this review, the possible Glu signaling methods are outlined in specific peripheral tissues including bone, testis, pancreas, and the adrenal, pituitary and pineal glands.
Topics: Amino Acid Transport System X-AG; Animals; Female; Glutamic Acid; Humans; Male; Mammals; Organ Specificity; Receptors, Glutamate; Signal Transduction
PubMed: 14686914
DOI: 10.1046/j.1432-1033.2003.03907.x -
Frontiers in Immunology 2022Exosomes are small extracellular vesicles that are secreted by almost all types of cells and exist in almost all extracellular spaces. As an important mediator of... (Review)
Review
Exosomes are small extracellular vesicles that are secreted by almost all types of cells and exist in almost all extracellular spaces. As an important mediator of intercellular communication, exosomes encapsulate the miRNA, lncRNA, cirRNA, mRNA, cytokine, enzyme, lipid, and other components from the cytoplasm into its closed single membrane structure and transfer them to recipient units in an autocrine, paracrine, or endocrine manner. Hypoxia is a state of low oxygen tension and is involved in many pathological processes. Hypoxia influences the size, quantity, and expression of exosome cargos. Exosomes derived from hypoxic tumor cells transfer genetics, proteins, and lipids to the recipient units to exert pleiotropic effects. Different donor cells produce different cargo contents, target different recipient units and lead to different biological effects. Hypoxic exosomes derived from tumor cells uptaken by normoxic tumor cells lead to promoted proliferation, migration, and invasion; uptaken by extracellular space or liver lead to promoted metastasis; uptaken by endothelial cells lead to promoted angiogenesis; uptaken by immune cells lead to promoted macrophage polarization and changed tumor immune microenvironment. In addition to various types of tumors, hypoxic exosomes also participate in the development of diseases in the cardiovascular system, neuron system, respiratory system, hematology system, endocrine system, urinary system, reproduction system, and skeletomuscular system. Understanding the special characteristics of hypoxic exosomes provide new insight into elaborating the pathogenesis of hypoxia related disease. This review summarizes hypoxia induced cargo changes and the biological effects of hypoxic exosomes in tumors and non-malignant diseases in different systems.
Topics: Cell Communication; Endothelial Cells; Exosomes; Humans; Hypoxia; Neoplasms; Tumor Microenvironment
PubMed: 35444652
DOI: 10.3389/fimmu.2022.824188