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Journal of the American Heart... Feb 2021The myocardium consists of different cell types, of which endothelial cells, cardiomyocytes, and fibroblasts are the most abundant. Communication between these different... (Review)
Review
The myocardium consists of different cell types, of which endothelial cells, cardiomyocytes, and fibroblasts are the most abundant. Communication between these different cell types, also called paracrine signaling, is essential for normal cardiac function, but also important in cardiac remodeling and heart failure. Systematic studies on the expression of ligands and their corresponding receptors in different cell types showed that for 60% of the expressed ligands in a particular cell, the receptor is also expressed. The fact that many ligand-receptor pairs are present in most cells, including the major cell types in the heart, indicates that autocrine signaling is a widespread phenomenon. Autocrine signaling in cardiac remodeling and heart failure is involved in all pathophysiological mechanisms generally observed: hypertrophy, fibrosis, angiogenesis, cell survival, and inflammation. Herein, we review ligand-receptor pairs present in the major cardiac cell types based on RNA-sequencing expression databases, and we review current literature on extracellular signaling proteins with an autocrine function in the heart; these include C-type natriuretic peptide, fibroblast growth factors 2, F21, and 23, macrophage migration inhibitory factor, heparin binding-epidermal growth factor, angiopoietin-like protein 2, leptin, adiponectin, follistatin-like 1, apelin, neuregulin 1, vascular endothelial growth factor, transforming growth factor β, wingless-type integration site family, member 1-induced secreted protein-1, interleukin 11, connective tissue growth factor/cellular communication network factor, and calcitonin gene‒related peptide. The large number of autocrine signaling factors that have been studied in the literature supports the concept that autocrine signaling is an essential part of myocardial biology and disease.
Topics: Animals; Autocrine Communication; Cells, Cultured; Heart Failure; Humans; Myocytes, Cardiac; Signal Transduction; Ventricular Remodeling
PubMed: 33470124
DOI: 10.1161/JAHA.120.019169 -
Cancer Biology & Therapy Dec 2023Vascular endothelial growth factor (VEGF) plays key roles in angiogenesis, vasculogenesis, and wound healing. In cancers, including triple negative breast cancer (TNBC),...
Vascular endothelial growth factor (VEGF) plays key roles in angiogenesis, vasculogenesis, and wound healing. In cancers, including triple negative breast cancer (TNBC), VEGF has been associated with increased invasion and metastasis, processes that require cancer cells to traverse through the extracellular matrix (ECM) and establish angiogenesis at distant sites. To further understand the role of VEGF in modifying the ECM, we characterized VEGF-mediated changes in the ECM of tumors derived from TNBC MDA-MB-231 cells engineered to overexpress VEGF. We established that increased VEGF expression by these cells resulted in tumors with reduced collagen 1 (Col1) fibers, fibronectin, and hyaluronan. Molecular characterization of tumors identified an increase of MMP1, uPAR, and LOX, and a decrease of MMP2, and ADAMTS1. α-SMA, a marker of cancer associated fibroblasts (CAFs), increased, and FAP-α, a marker of a subset of CAFs associated with immune suppression, decreased with VEGF overexpression. Analysis of human data from The Cancer Genome Atlas Program confirmed mRNA differences for several molecules when comparing TNBC with high and low VEGF expression. We additionally characterized enzymatic changes induced by VEGF overexpression in three different cancer cell lines that clearly identified autocrine-mediated changes, specifically uPAR, in these enzymes. Unlike the increase of Col1 fibers and fibronectin mediated by VEGF during wound healing, in the TNBC model, VEGF significantly reduced key protein components of the ECM. These results further expand our understanding of the role of VEGF in cancer progression and identify potential ECM-related targets to disrupt this progression.
Topics: Humans; Autocrine Communication; Extracellular Matrix; Fibronectins; Triple Negative Breast Neoplasms; Vascular Endothelial Growth Factor A
PubMed: 37389973
DOI: 10.1080/15384047.2023.2184145 -
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 -
International Journal of Molecular... Jan 2017Resistance to conventional chemotherapeutic agents, a typical feature of cholangiocarcinoma, prevents the efficacy of the therapeutic arsenal usually used to combat... (Review)
Review
Resistance to conventional chemotherapeutic agents, a typical feature of cholangiocarcinoma, prevents the efficacy of the therapeutic arsenal usually used to combat malignancy in humans. Mechanisms of chemoresistance by neoplastic cholangiocytes include evasion of drug-induced apoptosis mediated by autocrine and paracrine cues released in the tumor microenvironment. Here, recent evidence regarding molecular mechanisms of chemoresistance is reviewed, as well as associations between well-developed chemoresistance and activation of the cancer stem cell compartment. It is concluded that improved understanding of the complex interplay between apoptosis signaling and the promotion of cell survival represent potentially productive areas for active investigation, with the ultimate aim of encouraging future studies to unveil new, effective strategies able to overcome current limitations on treatment.
Topics: Autocrine Communication; Cell Line, Tumor; Cholangiocarcinoma; Drug Resistance, Neoplasm; Humans; Paracrine Communication; Stromal Cells
PubMed: 28098760
DOI: 10.3390/ijms18010149 -
The FEBS Journal Jan 2021The interface between the mammalian host and its environment is formed by barrier tissues, for example, of the skin, and the respiratory and the intestinal tracts. On... (Review)
Review
The interface between the mammalian host and its environment is formed by barrier tissues, for example, of the skin, and the respiratory and the intestinal tracts. On the one hand, barrier tissues are colonized by site-adapted microbial communities, and on the other hand, they contain specific myeloid cell networks comprising macrophages, dendritic cells, and granulocytes. These immune cells are tightly regulated in function and cell number, indicating important roles in maintaining tissue homeostasis and immune balance in the presence of commensal microorganisms. The regulation of myeloid cell density and activation involves cell-autonomous 'single-loop circuits' including autocrine mechanisms. However, an array of microenvironmental factors originating from nonimmune cells and the microbiota, as well as the microanatomical structure, impose additional layers of regulation onto resident myeloid cells. This review discusses models integrating these factors into cell-specific programs to instruct differentiation and proliferation best suited for the maintenance and renewal of immune homeostasis in the tissue-specific environment.
Topics: Animals; Autocrine Communication; Cell Count; Cell Differentiation; Cell Proliferation; Cytokines; Dendritic Cells; Granulocytes; Homeostasis; Humans; Immunity, Innate; Intestinal Mucosa; Macrophages; Microbiota; Models, Immunological; Respiratory Mucosa; Skin; Symbiosis
PubMed: 32502309
DOI: 10.1111/febs.15436 -
Diabetes, Obesity & Metabolism Sep 2014Pulsatile secretion is an inherent property of hormone-releasing pancreatic islet cells. This secretory pattern is physiologically important and compromised in diabetes.... (Review)
Review
Pulsatile secretion is an inherent property of hormone-releasing pancreatic islet cells. This secretory pattern is physiologically important and compromised in diabetes. Neurotransmitters released from islet cells may shape the pulses in auto/paracrine feedback loops. Within islets, glucose-stimulated β-cells couple via gap junctions to generate synchronized insulin pulses. In contrast, α- and δ-cells lack gap junctions, and glucagon release from islets stimulated by lack of glucose is non-pulsatile. Increasing glucose concentrations gradually inhibit glucagon secretion by α-cell-intrinsic mechanism/s. Further glucose elevation will stimulate pulsatile insulin release and co-secretion of neurotransmitters. Excitatory ATP may synchronize β-cells with δ-cells to generate coinciding pulses of insulin and somatostatin. Inhibitory neurotransmitters from β- and δ-cells can then generate antiphase pulses of glucagon release. Neurotransmitters released from intrapancreatic ganglia are required to synchronize β-cells between islets to coordinate insulin pulsatility from the entire pancreas, whereas paracrine intra-islet effects still suffice to explain coordinated pulsatile release of glucagon and somatostatin. The present review discusses how neurotransmitters contribute to the pulsatility at different levels of integration.
Topics: Animals; Appetite Regulation; Autocrine Communication; Biogenic Monoamines; Calcium Signaling; Feedback, Physiological; Glucagon; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Kinetics; Models, Biological; Neurons; Somatostatin; Synaptic Transmission
PubMed: 25200303
DOI: 10.1111/dom.12345 -
Molecular and Cellular Biochemistry Jan 2022Several benefits can be acquired through physical exercise. Different classes of biomolecules are responsible for the cross-talk between distant organs. The secretome of... (Review)
Review
Several benefits can be acquired through physical exercise. Different classes of biomolecules are responsible for the cross-talk between distant organs. The secretome of skeletal muscles, and more widely the field of organokines, is ever-expanding. "Exerkine" has emerged as the umbrella term covering any humoral factors secreted into circulation by tissues in response to exercise. This review aims at describing the most interesting exerkines discovered in the last 3 years, which are paving the way for both physiological novel insights and potential medical strategies. The five exerkines identified all play a significant role in the healthy effect of exercise. Specifically: miR-1192, released by muscles and myocardium into circulation, by modulating cardioprotective effect in trained mice; miR-342-5p, located into exosomes from vascular endothelial cells, also a cardioprotective miRNA in trained young humans; apelin, released by muscles into circulation, involved in anti-inflammatory pathways and muscle regenerative capacity in rats; GDF-15, released into circulation from yet unknown source, whose effects can be observed on multiple organs in young men after a single bout of exercise; oxytocin, released by myoblasts and myotubes, with autocrine and paracrine functions in myotubes. The systemic transport by vesicles and the crosstalk between distant organs deserve a deep investigation. Sources, targets, transport mechanisms, biological roles, population samples, frequency, intensity, time and type of exercise should be considered for the characterization of existing and novel exerkines. The "exercise is medicine" framework should include exerkines in favor of novel insights for public health.
Topics: Animals; Apelin; Autocrine Communication; Circulating MicroRNA; Endothelial Cells; Growth Differentiation Factor 15; Humans; Mice; Muscle, Skeletal; Paracrine Communication; Rats; Regeneration
PubMed: 34554363
DOI: 10.1007/s11010-021-04264-5 -
Current Osteoporosis Reports Oct 2017In addition to the actions of the endocrine hormone, 1alpha,25-dihydroxyvitamin D (1,25(OH)D) in stimulating intestinal calcium absorption, the regulation of bone... (Review)
Review
PURPOSE OF REVIEW
In addition to the actions of the endocrine hormone, 1alpha,25-dihydroxyvitamin D (1,25(OH)D) in stimulating intestinal calcium absorption, the regulation of bone mineral metabolism by 1,25(OH)D is also considered an important contributor to calcium homeostasis. However, recent evidence suggest that 1,25(OH)D acting either via endocrine or autocrine pathways plays varied roles in bone, which suggests that vitamin D contributes to the maintenance of bone mineral in addition to its catabolic roles. This review highlights the contrasting evidence for the direct action for vitamin D metabolism and activity in bone.
RECENT FINDINGS
Numerous cells within bone express vitamin D receptor (VDR), synthesise and catabolise 1,25(OH)D via 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1), and 25-hydroxyvitamin D 24-hydroxylase (CYP24A1) enzymes, respectively. Recent evidence suggests that all three genes are required to regulate processes of bone resorption, mineralization and fracture repair. The actions of vitamin D in bone appear to negatively or positively regulate bone mineral depending on the physiological and pathological circumstances, suggesting that vitamin D plays pleiotropic roles in bone.
Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Autocrine Communication; Bone Resorption; Bone and Bones; Calcification, Physiologic; Fracture Healing; Humans; Receptors, Calcitriol; Vitamin D; Vitamin D3 24-Hydroxylase
PubMed: 28808890
DOI: 10.1007/s11914-017-0394-8 -
Seminars in Cancer Biology Dec 2019The phosphoinositide 3-kinase (PI3K) pathway, one of the most commonly activated signaling pathways in human cancers, plays a crucial role in the regulation of cell... (Review)
Review
The phosphoinositide 3-kinase (PI3K) pathway, one of the most commonly activated signaling pathways in human cancers, plays a crucial role in the regulation of cell proliferation, differentiation, and survival. This pathway is usually activated by receptor tyrosine kinases (RTKs), whose constitutive and aberrant activation is via gain-of-function mutations, chromosomal rearrangement, gene amplification and autocrine. Blockage of PI3K pathway by targeted therapy on RTKs with tyrosine kinases inhibitors (TKIs) and monoclonal antibodies (mAbs) has achieved great progress in past decades; however, there still remain big challenges during their clinical application. In this review, we provide an overview about the most frequently encountered alterations in RTKs and focus on current therapeutic agents developed to counteract their aberrant functions, accompanied with discussions of two major challenges to the RTKs-targeted therapy in cancer - resistance and toxicity.
Topics: Animals; Antineoplastic Agents; Autocrine Communication; Biomarkers, Tumor; Chromosome Aberrations; Enzyme Activation; Gene Expression Regulation, Neoplastic; Humans; Molecular Targeted Therapy; Mutation; Neoplasms; Phosphatidylinositol 3-Kinases; Protein Binding; Protein Interaction Domains and Motifs; Protein Kinase Inhibitors; Signal Transduction
PubMed: 30943434
DOI: 10.1016/j.semcancer.2019.03.006 -
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