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Current Opinion in Cell Biology Apr 2020Physiological functions depend on a coordinated interplay of numerous different cell types. Proteins serve as major signaling molecules between cells; however, their... (Review)
Review
Physiological functions depend on a coordinated interplay of numerous different cell types. Proteins serve as major signaling molecules between cells; however, their comprehensive investigation in physiologically relevant settings has remained challenging. Mass spectrometry (MS)-based shotgun proteomics is emerging as a powerful technology for the systematic analysis of protein-mediated intercellular signaling and regulated post-translational modifications. Here, we discuss recent advancements in cell biological, chemical, and biochemical MS-based approaches for the profiling of cellular messengers released by sending cells, receptors expressed on the cell surface, and their interactions. We highlight methods tailored toward the mapping of dynamic signal transduction mechanisms at cellular interfaces and approaches to dissect communication cell specifically in heterocellular systems. Thereby, MS-based proteomics contributes a unique systems biology perspective for the identification of intercellular signaling pathways deregulated in disease.
Topics: Humans; Mass Spectrometry; Protein Processing, Post-Translational; Proteomics; Signal Transduction
PubMed: 31927463
DOI: 10.1016/j.ceb.2019.12.002 -
Trends in Immunology Jan 2022Catestatin (CST) is a bioactive cleavage product of the neuroendocrine prohormone chromogranin A (CgA). Recent findings show that CST can exert anti-inflammatory and... (Review)
Review
Catestatin (CST) is a bioactive cleavage product of the neuroendocrine prohormone chromogranin A (CgA). Recent findings show that CST can exert anti-inflammatory and antiadrenergic effects by suppressing the inflammatory actions of mammalian macrophages. However, recent findings also suggest that macrophages themselves are major CST producers. Here, we hypothesize that macrophages produce CST in an inflammation-dependent manner and thereby might self-regulate inflammation in an autocrine fashion. CST is associated with pathological conditions hallmarked by chronic inflammation, including autoimmune, cardiovascular, and metabolic disorders. Since intraperitoneal injection of CST in mouse models of diabetes and inflammatory bowel disease has been reported to be beneficial for mitigating disease, we posit that CST should be further investigated as a candidate target for treating certain inflammatory diseases.
Topics: Animals; Chromogranin A; Humans; Inflammation; Macrophages; Mammals; Mice; Peptide Fragments
PubMed: 34844850
DOI: 10.1016/j.it.2021.11.002 -
Frontiers in Endocrinology 2023With increasing life expectancy, the related disorders of bone loss, metabolic dysregulation and sarcopenia have become major health threats to the elderly. Each of... (Review)
Review
With increasing life expectancy, the related disorders of bone loss, metabolic dysregulation and sarcopenia have become major health threats to the elderly. Each of these conditions is prevalent in patients with chronic kidney disease (CKD), particularly in more advanced stages. Our current understanding of the bone-muscle interaction is beyond mechanical coupling, where bone and muscle have been identified as interrelated secretory organs, and regulation of both bone and muscle metabolism occurs through osteokines and myokines autocrine, paracrine and endocrine systems. This review appraises the current knowledge regarding biochemical crosstalk between bone and muscle, and considers recent progress related to the role of osteokines and myokines in CKD, including modulatory effects of physical exercise and potential therapeutic targets to improve musculoskeletal health in CKD patients.
Topics: Humans; Aged; Muscle, Skeletal; Sarcopenia; Bone and Bones; Cell Physiological Phenomena; Bone Diseases, Metabolic
PubMed: 37033253
DOI: 10.3389/fendo.2023.1146868 -
Atherosclerosis Jun 2022As one of the cornerstones of innate immunity, the complement system has long been implicated in the pathogenesis of atherosclerosis. Growing evidence demonstrates the... (Review)
Review
As one of the cornerstones of innate immunity, the complement system has long been implicated in the pathogenesis of atherosclerosis. Growing evidence demonstrates the presence of complement activation products in human atherosclerotic plaques, where they can exhibit both protective and proatherogenic properties as supported by numerous experimental findings. While complement initiation resulting in the cleavage of the central complement component C3 appears to have a crucial role in tempering lesion progression by aiding the clearance of apoptotic cells, cascade propagation to the terminal pathway characterized by C5 cleavage and membrane attack complex formation may promote plaque vulnerability. Nevertheless, these assumptions are made based on studies focusing predominantly on systemic, liver-derived complement, whereas it is now evident that almost every cell type can produce complement proteins and the site of synthesis can dictate the function of complement. However, the role of local complement activation in lesion formation remains largely understudied. Here, we review the current literature on complement activation in human atherosclerotic plaques, discuss clinical and genetic associations between complement and cardiovascular disease susceptibility and summarize experimental evidence gained from animal studies. Furthermore, by highlighting recent findings with respect to extrahepatic complement production in the artery wall, we illustrate the necessity to uncover the contribution of local (paracrine, autocrine as well as intracellular) vis-à-vis systemic complement activation to atherosclerotic lesion formation.
Topics: Animals; Atherosclerosis; Complement Activation; Complement C3; Complement System Proteins; Immunity, Innate; Plaque, Atherosclerotic
PubMed: 35365353
DOI: 10.1016/j.atherosclerosis.2022.03.014 -
Trends in Molecular Medicine Jan 2021Human skin responds to numerous neurohormones, neuropeptides, and neurotransmitters that reach it via the vasculature or skin nerves, and/or are generated... (Review)
Review
Human skin responds to numerous neurohormones, neuropeptides, and neurotransmitters that reach it via the vasculature or skin nerves, and/or are generated intracutaneously, thus acting in a para- and autocrine manner. This review focuses on how neurohormones impact on human skin physiology and pathology. We highlight basic concepts, major open questions, and translational research perspectives in cutaneous neuroendocrinology and argue that greater emphasis on neuroendocrine human skin research will foster the development of novel dermatological therapies. Furthermore, human skin and its appendages can be used as highly accessible and clinically relevant model systems for probing nonclassical, ancestral neurohormone functions. This calls for close interdisciplinary collaboration between dermatologists, skin biologists, neuroendocrinologists, and neuropharmacologists.
Topics: Dermatology; Endocrinology; Humans; Neuroendocrinology; Skin; Skin Physiological Phenomena; Translational Research, Biomedical
PubMed: 32981840
DOI: 10.1016/j.molmed.2020.09.002 -
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 -
Biomolecules Apr 2022Fibrosis is often the end result of chronic inflammation. It is characterized by the excessive deposition of extracellular matrix. This leads to structural alterations... (Review)
Review
Fibrosis is often the end result of chronic inflammation. It is characterized by the excessive deposition of extracellular matrix. This leads to structural alterations in the tissue, causing permanent damage and organ dysfunction. Depending on the organ it effects, fibrosis can be a serious threat to human life. The molecular mechanism of fibrosis is still not fully understood, but the NLRP3 (NOD-, LRR- and pyrin-domain-containing protein 3) inflammasome appears to play a significant role in the pathogenesis of fibrotic disease. The NLRP3 inflammasome has been the most extensively studied inflammatory pathway to date. It is a crucial component of the innate immune system, and its activation mediates the secretion of interleukin (IL)-1β and IL-18. NLRP3 activation has been strongly linked with fibrosis and drives the differentiation of fibroblasts into myofibroblasts by the chronic upregulation of IL-1β and IL-18 and subsequent autocrine signaling that maintains an activated inflammasome. Both IL-1β and IL-18 are profibrotic, however IL-1β can have antifibrotic capabilities. NLRP3 responds to a plethora of different signals that have a common but unidentified unifying trigger. Even after 20 years of extensive investigation, regulation of the NLRP3 inflammasome is still not completely understood. However, what is known about NLRP3 is that its regulation and activation is complex and not only driven by various activators but controlled by numerous post-translational modifications. More recently, there has been an intensive attempt to discover NLRP3 inhibitors to treat chronic diseases. This review addresses the role of the NLRP3 inflammasome in fibrotic disorders across many different tissues. It discusses the relationships of various NLRP3 activators to fibrosis and covers different therapeutics that have been developed, or are currently in development, that directly target NLRP3 or its downstream products as treatments for fibrotic disorders.
Topics: Fibrosis; Humans; Inflammasomes; Interleukin-18; Myofibroblasts; NLR Family, Pyrin Domain-Containing 3 Protein
PubMed: 35625564
DOI: 10.3390/biom12050634 -
Current Diabetes Reviews 2020Adiponectin is an adipocyte-derived cytokine closely associated with obesity, altered body adipose tissue distribution, insulin resistance, and cardiovascular diseases. (Review)
Review
BACKGROUND
Adiponectin is an adipocyte-derived cytokine closely associated with obesity, altered body adipose tissue distribution, insulin resistance, and cardiovascular diseases.
INTRODUCTION
Evidence from animal and human studies demonstrate that adiponectin plays an important role in the regulation of glucose and lipid metabolism. Adiponectin increases insulin sensitivity and improves systemic lipid metabolism. Although research efforts on adiponectin mostly aim towards its endocrine functions, this adipocyte-derived molecule also has profound autocrine and paracrine functions.
CONCLUSION
In this review, our aim is to discuss the role of adiponectin in maintaining metabolic homeostasis and its association with cardiovascular health. The proper identification of these roles is of great importance, which has the potential to identify a wealth of novel targets for the treatment of diabetes and related cardio-metabolic diseases.
Topics: Adiponectin; Adipose Tissue; Animals; Cardiovascular Diseases; Cell Communication; Central Nervous System; Diabetes Mellitus; Energy Metabolism; Glucose; Homeostasis; Humans; Insulin Resistance; Insulin-Secreting Cells; Lipid Metabolism; Obesity
PubMed: 31267874
DOI: 10.2174/1573399815666190702155733 -
Journal of Molecular Neuroscience : MN May 2020Cytokines are proteins secreted by diverse types of immune and non-immune cells and play a role in the communication between the immune and nervous systems. Cytokines... (Review)
Review
Cytokines are proteins secreted by diverse types of immune and non-immune cells and play a role in the communication between the immune and nervous systems. Cytokines include lymphokines, monokines, chemokines, interleukins, interferons, colony stimulating factors, and growth factors. They can be both pro- and anti-inflammatory and have autocrine, paracrine, and endocrine activities. These proteins are involved in initiation and persistence of pain, and the progress of hyperalgesia and allodynia, upon stimulating nociceptive sensory neurons, and inducing central sensitization. The objective of this review is to discuss several types of pro- and anti-inflammatory mediators and their relation with inflammatory pain in masticatory muscles.
Topics: Animals; Craniomandibular Disorders; Facial Pain; Humans; Inflammation Mediators; Interleukins; Masticatory Muscles
PubMed: 32008162
DOI: 10.1007/s12031-020-01491-1 -
Molecules (Basel, Switzerland) Jan 2022Neuropeptides are autocrine and paracrine signalling factors and mainly bind to G protein-coupled receptors (GPCRs) to trigger intracellular secondary messenger release... (Review)
Review
Neuropeptides are autocrine and paracrine signalling factors and mainly bind to G protein-coupled receptors (GPCRs) to trigger intracellular secondary messenger release including adenosine 3', 5'-cyclic monophosphate (cAMP), thus modulating cancer progress in different kind of tumours. As one of the downstream effectors of cAMP, exchange proteins directly activated by cAMP (EPACs) play dual roles in cancer proliferation and metastasis. More evidence about the relationship between neuropeptides and EPAC pathways have been proposed for their potential role in cancer development; hence, this review focuses on the role of neuropeptide/GPCR system modulation of cAMP/EPACs pathways in cancers. The correlated downstream pathways between neuropeptides and EPACs in cancer cell proliferation, migration, and metastasis is discussed to glimmer the direction of future research.
Topics: Animals; Biomarkers; Cyclic AMP; Disease Susceptibility; Gene Expression Regulation, Neoplastic; Guanine Nucleotide Exchange Factors; Humans; Neoplasms; Neuropeptides; Organ Specificity; Protein Binding; Receptors, Neurotransmitter; Signal Transduction
PubMed: 35011543
DOI: 10.3390/molecules27010311