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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 -
Oncogene Mar 2001Autocrine and paracrine signaling leading to stimulation of tumor cell growth is a common theme in human cancers. In addition to polypeptide growth factors such as EGF... (Review)
Review
Autocrine and paracrine signaling leading to stimulation of tumor cell growth is a common theme in human cancers. In addition to polypeptide growth factors such as EGF family members which signal through receptor tyrosine kinases, accumulating evidence supports the autocrine and paracrine involvement of specific neuropeptides with defined physiologic actions as neurotransmitters and gut hormones in lung, gastric, colorectal, pancreatic and prostatic cancers. These neuropeptides, including gastrin-releasing peptide, neuromedin B, neurotensin, gastrin, cholecystokinin and arginine vasopressin bind seven transmembrane-spanning receptors that couple to heterotrimeric G proteins. Studies with human small cell lung cancer (SCLC) cells support a requirement for balanced signaling through G(q) and G(12/13) proteins leading to intracellular Ca2+ mobilization, PKC activation and regulation of the ERK and JNK MAP kinase pathways. While specific neuropeptide antagonists offer promise for interrupting the single neuropeptide autocrine systems operating in pancreatic and prostatic cancers, SCLC is exemplified by multiple, redundant neuropeptide autocrine systems such that tumor growth cannot be inhibited with a single specific antagonist. However, a novel class of neuropeptide derivatives based on the substance P sequence have been defined that exhibit broad specificity for neuropeptide receptors and induce apoptosis in SCLC by functioning as biased agonists that stimulate discordant signal transduction. Thus, interruption of autocrine and paracrine neuropeptide signaling with specific antagonists or broad-spectrum biased agonists offer promising new therapeutic approaches to the treatment of human cancers.
Topics: Antineoplastic Agents; Autocrine Communication; Cell Transformation, Neoplastic; Humans; Models, Biological; Paracrine Communication; Receptors, Neuropeptide; Signal Transduction; Substance P
PubMed: 11313903
DOI: 10.1038/sj.onc.1204183 -
Neuroendocrinology 2023Extracellular vesicles (EVs) are membrane-enclosed nanoparticles that contain various biomolecules, including nucleic acids, proteins and lipids, and are manufactured... (Review)
Review
Extracellular vesicles (EVs) are membrane-enclosed nanoparticles that contain various biomolecules, including nucleic acids, proteins and lipids, and are manufactured and released by virtually all cell types. There is evidence that EVs are involved in intercellular communication, acting in an autocrine, paracrine or/and endocrine manner. EVs are released by the cells of the central nervous system (CNS), including neurons, astrocytes, oligodendrocytes and microglia, and have the ability to cross the blood-brain barrier (BBB) and enter the systemic circulation. Neuroendocrine cells are specialized neurons that secrete hormones directly into blood vessels, such as the hypophyseal portal system or the systemic circulation, a process that allows neuroendocrine integration to take place. In mammals, neuroendocrine cells are widely distributed throughout various anatomic compartments, with the hypothalamus being a central neuroendocrine integrator. The hypothalamus is a key part of the stress system (SS), a highly conserved neuronal/neuroendocrine system aiming at maintaining systemic homeostasis when the latter is threatened by various stressors. The central parts of the SS are the interconnected hypothalamic corticotropin-releasing hormone (CRH) and the brainstem locus caeruleus-norepinephrine (LC-NE) systems, while their peripheral parts are, respectively, the pituitary-adrenal axis and the sympathetic nervous/sympatho-adrenomedullary systems (SNS-SAM) as well as components of the parasympathetic nervous system (PSNS). During stress, multiple CNS loci show plasticity and undergo remodeling, partly mediated by increased glutamatergic and noradrenergic activity, and the actions of cytokines and glucocorticoids, all regulated by the interaction of the hypothalamic-pituitary-adrenal (HPA) axis and the LC-NE/SNS-SAM systems. In addition, there are peripheral changes due to the increased secretion of stress hormones and pro-inflammatory cytokines in the context of stress-related systemic (para)inflammation. We speculate that during stress, central and peripheral, cellular and molecular alterations take place, with some of them generated, communicated, and spread via the release of stress-induced neural/neuroendocrine cell-derived EVs.
Topics: Animals; Hypothalamo-Hypophyseal System; Neurosecretory Systems; Adrenocorticotropic Hormone; Norepinephrine; Extracellular Vesicles; Cytokines; Pituitary-Adrenal System; Stress, Physiological; Corticotropin-Releasing Hormone; Mammals
PubMed: 36137504
DOI: 10.1159/000527182 -
Physiological Reviews Jul 2020Autocrine and paracrine signaling in the kidney adds an extra level of diversity and complexity to renal physiology. The extensive scientific production on the topic... (Review)
Review
Autocrine and paracrine signaling in the kidney adds an extra level of diversity and complexity to renal physiology. The extensive scientific production on the topic precludes easy understanding of the fundamental purpose of the vast number of molecules and systems that influence the renal function. This systematic review provides the broader pen strokes for a collected image of renal paracrine signaling. First, we recapitulate the essence of each paracrine system one by one. Thereafter the single components are merged into an overarching physiological concept. The presented survey shows that despite the diversity in the web of paracrine factors, the collected effect on renal function may not be complicated after all. In essence, paracrine activation provides an intelligent system that perceives minor perturbations and reacts with a coordinated and integrated tissue response that relieves the work load from the renal epithelia and favors diuresis and natriuresis. We suggest that the overall function of paracrine signaling is reno-protection and argue that renal paracrine signaling and self-regulation are two sides of the same coin. Thus local paracrine signaling is an intrinsic function of the kidney, and the overall renal effect of changes in blood pressure, volume load, and systemic hormones will always be tinted by its paracrine status.
Topics: Animals; Autocrine Communication; Humans; Kidney; Paracrine Communication; Signal Transduction
PubMed: 31999508
DOI: 10.1152/physrev.00014.2019 -
Cancer Cells (Cold Spring Harbor, N.Y.... Sep 1989Autocrine growth factor loops ensure the continued growth of neoplastic cells. According to the traditional view of such autocrine loops, receptor binding and... (Review)
Review
Autocrine growth factor loops ensure the continued growth of neoplastic cells. According to the traditional view of such autocrine loops, receptor binding and transduction of a mitogenic signal occur when a growth factor is secreted and subsequently interacts with its receptor on the surface of the secreting or neighboring cells. For several growth factors there is now evidence that the mitogenic signal may be transduced without factor secretion. In these instances, the growth factor appears to interact with its receptor intracellularly, creating in effect a "private" autocrine loop. We will discuss three growth factors that may operate by the latter mechanism, as well as two that rely instead on classical "public" autocrine loops, where the growth factor must be secreted and is therefore accessible to neighboring cells. We also consider the properties of these growth factor/receptor systems that may determine their involvement in either type of autocrine loop.
Topics: Amino Acid Sequence; Animals; Growth Substances; Molecular Sequence Data; Neoplasms
PubMed: 2701363
DOI: No ID Found -
Current Opinion in Neurobiology Aug 2018Although retrograde neurotrophin signaling has provided an immensely influential paradigm for understanding growth factor signaling in the nervous system, recent studies... (Review)
Review
Although retrograde neurotrophin signaling has provided an immensely influential paradigm for understanding growth factor signaling in the nervous system, recent studies indicate that growth factors also signal via cell-autonomous, or autocrine, mechanisms. Autocrine signals have been discovered in many neuronal contexts, providing insights into their regulation and function. The growing realization of the importance of cell-autonomous signaling stems from advances in both conditional genetic approaches and in sophisticated analyses of growth factor dynamics, which combine to enable rigorous in vivo dissection of signaling pathways. Here we review recent studies defining autocrine roles for growth factors such as BDNF, and classical morphogens, including Wnts and BMPs, in regulating neuronal development and plasticity. Collectively, these studies highlight an intimate relationship between activity-dependent autocrine signaling and synaptic plasticity, and further suggest a common principle for coordinating paracrine and autocrine signaling in the nervous system.
Topics: Animals; Autocrine Communication; Neurons; Signal Transduction
PubMed: 29547843
DOI: 10.1016/j.conb.2018.03.002 -
Physiological Reviews Jul 2006Since the first identification of renin by Tigerstedt and Bergmann in 1898, the renin-angiotensin system (RAS) has been extensively studied. The current view of the... (Review)
Review
Since the first identification of renin by Tigerstedt and Bergmann in 1898, the renin-angiotensin system (RAS) has been extensively studied. The current view of the system is characterized by an increased complexity, as evidenced by the discovery of new functional components and pathways of the RAS. In recent years, the pathophysiological implications of the system have been the main focus of attention, and inhibitors of the RAS such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin (ANG) II receptor blockers have become important clinical tools in the treatment of cardiovascular and renal diseases such as hypertension, heart failure, and diabetic nephropathy. Nevertheless, the tissue RAS also plays an important role in mediating diverse physiological functions. These focus not only on the classical actions of ANG on the cardiovascular system, namely, the maintenance of cardiovascular homeostasis, but also on other functions. Recently, the research efforts studying these noncardiovascular effects of the RAS have intensified, and a large body of data are now available to support the existence of numerous organ-based RAS exerting diverse physiological effects. ANG II has direct effects at the cellular level and can influence, for example, cell growth and differentiation, but also may play a role as a mediator of apoptosis. These universal paracrine and autocrine actions may be important in many organ systems and can mediate important physiological stimuli. Transgenic overexpression and knock-out strategies of RAS genes in animals have also shown a central functional role of the RAS in prenatal development. Taken together, these findings may become increasingly important in the study of organ physiology but also for a fresh look at the implications of these findings for organ pathophysiology.
Topics: Animals; Endocrine System; Humans; Renin-Angiotensin System
PubMed: 16816138
DOI: 10.1152/physrev.00036.2005 -
Cancers Feb 2020Insulin receptor overexpression is a common event in human cancer. Its overexpression is associated with a relative increase in the expression of its isoform A (IR), a... (Review)
Review
Insulin receptor overexpression is a common event in human cancer. Its overexpression is associated with a relative increase in the expression of its isoform A (IR), a shorter variant lacking 11 aa in the extracellular domain, conferring high affinity for the binding of IGF-II along with added intracellular signaling specificity for this ligand. Since IGF-II is secreted by the vast majority of malignant solid cancers, where it establishes autocrine stimuli, the co-expression of IGF-II and IR in cancer provides specific advantages such as apoptosis escape, growth, and proliferation to those cancers bearing such a co-expression pattern. However, little is known about the exact role of this autocrine ligand-receptor system in sustaining cancer malignant features such as angiogenesis, invasion, and metastasis. The recent finding that the overexpression of angiogenic receptor kinase EphB4 along with VEGF-A is tightly dependent on the IGF-II/IR autocrine system independently of IGFIR provided new perspectives for all malignant IGF2omas (those aggressive solid cancers secreting IGF-II). The present review provides an updated view of the IGF system in cancer, focusing on the biology of the autocrine IGF-II/IR ligand-receptor axis and supporting its underscored role as a malignant-switch checkpoint target.
PubMed: 32033443
DOI: 10.3390/cancers12020366 -
Methods in Molecular Biology (Clifton,... 2012During the 1970s, domestic animal biotechnology, i.e., embryo transfer in farm animals, was confronted with the problem of embryonic developmental arrest observed in...
During the 1970s, domestic animal biotechnology, i.e., embryo transfer in farm animals, was confronted with the problem of embryonic developmental arrest observed in vitro, especially during the cycle in which maternal to zygotic transition (MZT) cycle takes place. In farm animals, obtaining blastocysts is mandatory, as transfer at earlier stages results in expulsion of the embryo from the vagina. In humans, the first attempts to obtain blastocysts with classical culture media were disappointing, and the use of a coculture strategy was naturally tempting: the first significant results of successful blastocyst development were obtained in the early 1980s, using trophoblastic tissue as a feeder layer in order to mimic an autocrine embryotrophic system. The next supporting cell systems were based on oviduct epithelial cells and uterine cells in order to achieve a paracrine effect. Non-hormone dependence was then demonstrated with the use of prepubertal cells, and finally with the use of established cell lines of nongenital origin (African Green Monkey Kidney, Vero cells). The embryotrophic properties are linked to features of "transport epithelia." Vero cells have been extensively used in human ART, and most of our knowledge about the human blastocyst was gathered with the use of this technology. Coculture is still in current use, but with systems that employ autologous uterine cells. Results following the use of this technology in human ART are superior to those observed with the use of sequential media. The benefit is linked to the release of free radical scavengers and growth factors by the feeder cells. In animal biotechnology, an important part of the "precious embryos," i.e., those resulting from cloning technology, involves coculture with buffalo rat liver (BRL) cells or Vero cells.
Topics: Animals; Blastocyst; Chlorocebus aethiops; Cryopreservation; Embryo Culture Techniques; Female; Humans; Uterus; Vero Cells
PubMed: 22829378
DOI: 10.1007/978-1-61779-971-6_14 -
Neuroimmunomodulation 2024The brain and the immune systems represent the two primary adaptive systems within the body. Both are involved in a dynamic process of communication, vital for the... (Review)
Review
BACKGROUND
The brain and the immune systems represent the two primary adaptive systems within the body. Both are involved in a dynamic process of communication, vital for the preservation of mammalian homeostasis. This interplay involves two major pathways: the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system.
SUMMARY
The establishment of infection can affect immunoneuroendocrine interactions, with functional consequences for immune organs, particularly the thymus. Interestingly, the physiology of this primary organ is not only under the control of the central nervous system (CNS) but also exhibits autocrine/paracrine regulatory circuitries mediated by hormones and neuropeptides that can be altered in situations of infectious stress or chronic inflammation. In particular, Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), impacts upon immunoneuroendocrine circuits disrupting thymus physiology. Here, we discuss the most relevant findings reported in relation to brain-thymic connections during T. cruzi infection, as well as their possible implications for the immunopathology of human Chagas disease.
KEY MESSAGES
During T. cruzi infection, the CNS influences thymus physiology through an intricate network involving hormones, neuropeptides, and pro-inflammatory cytokines. Despite some uncertainties in the mechanisms and the fact that the link between these abnormalities and chronic Chagasic cardiomyopathy is still unknown, it is evident that the precise control exerted by the brain over the thymus is markedly disrupted throughout the course of T. cruzi infection.
Topics: Humans; Chagas Disease; Animals; Brain; Thymus Gland; Trypanosoma cruzi; Hypothalamo-Hypophyseal System; Neuroimmunomodulation; Pituitary-Adrenal System
PubMed: 38527434
DOI: 10.1159/000538220