scholarly journals Secretomics to Discover Regulators in Diseases

2019 ◽  
Vol 20 (16) ◽  
pp. 3893 ◽  
Author(s):  
Parkyong Song ◽  
Yonghoon Kwon ◽  
Jae-Yeol Joo ◽  
Do-Geun Kim ◽  
Jong Hyuk Yoon
Keyword(s):  
Metabolic Diseases ◽  
Cell Communication ◽  
Secretory Proteins ◽  
Cytokines And Chemokines ◽  
Intracellular Proteins ◽  
New Research ◽  
Neural Diseases ◽  
Peptide Preparation ◽  
Secretome Profiling ◽  
Powerful Strategy

Secretory proteins play important roles in the cross-talk of individual functional units, including cells. Since secretory proteins are essential for signal transduction, they are closely related with disease development, including metabolic and neural diseases. In metabolic diseases, adipokines, myokines, and hepatokines are secreted from respective organs under specific environmental conditions, and play roles in glucose homeostasis, angiogenesis, and inflammation. In neural diseases, astrocytes and microglia cells secrete cytokines and chemokines that play roles in neurotoxic and neuroprotective responses. Mass spectrometry-based secretome profiling is a powerful strategy to identify and characterize secretory proteins. This strategy involves stepwise processes such as the collection of conditioned medium (CM) containing secretome proteins and concentration of the CM, peptide preparation, mass analysis, database search, and filtering of secretory proteins; each step requires certain conditions to obtain reliable results. Proteomic analysis of extracellular vesicles has become a new research focus for understanding the additional extracellular functions of intracellular proteins. Here, we provide a review of the insights obtained from secretome analyses with regard to disease mechanisms, and highlight the future prospects of this technology. Continued research in this field is expected to provide valuable information on cell-to-cell communication and uncover new pathological mechanisms.

scholarly journals Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1004
Author(s):  
Sonia Kiran ◽  
Vijay Kumar ◽  
Santosh Kumar ◽  
Robert L Price ◽  
Udai P. Singh
Keyword(s):  
Insulin Resistance ◽  
Immune Response ◽  
T Cells ◽  
Immune Cells ◽  
Metabolic Diseases ◽  
Liver Disorder ◽  
Low Grade ◽  
Peripheral Tissues ◽  
Nonalcoholic Fatty Liver ◽  
Cytokines And Chemokines

Obesity is characterized as a complex and multifactorial excess accretion of adipose tissue (AT) accompanied with alterations in the immune response that affects virtually all age and socioeconomic groups around the globe. The abnormal accumulation of AT leads to several metabolic diseases, including nonalcoholic fatty liver disorder (NAFLD), low-grade inflammation, type 2 diabetes mellitus (T2DM), cardiovascular disorders (CVDs), and cancer. AT is an endocrine organ composed of adipocytes and immune cells, including B-Cells, T-cells and macrophages. These immune cells secrete various cytokines and chemokines and crosstalk with adipokines to maintain metabolic homeostasis and low-grade chronic inflammation. A novel form of adipokines, microRNA (miRs), is expressed in many developing peripheral tissues, including ATs, T-cells, and macrophages, and modulates the immune response. miRs are essential for insulin resistance, maintaining the tumor microenvironment, and obesity-associated inflammation (OAI). The abnormal regulation of AT, T-cells, and macrophage miRs may change the function of different organs including the pancreas, heart, liver, and skeletal muscle. Since obesity and inflammation are closely associated, the dysregulated expression of miRs in inflammatory adipocytes, T-cells, and macrophages suggest the importance of miRs in OAI. Therefore, in this review article, we have elaborated the role of miRs as epigenetic regulators affecting adipocyte differentiation, immune response, AT browning, adipogenesis, lipid metabolism, insulin resistance (IR), glucose homeostasis, obesity, and metabolic disorders. Further, we will discuss a set of altered miRs as novel biomarkers for metabolic disease progression and therapeutic targets for obesity.

scholarly journals Metabolism of Epithelial Cells in Health and Allergic Disease: Collegium Internationale Allergologicum Update 2021

2021 ◽  
pp. 1-16
Author(s):  
Ashley M. Queener ◽  
Sergio E. Chiarella ◽  
Lyda Cuervo-Pardo ◽  
Mackenzie E. Coden ◽  
Hiam Abdala-Valencia ◽  
...  
Keyword(s):  
Allergic Disease ◽  
Clinical Evidence ◽  
Metabolic Diseases ◽  
Tricarboxylic Acid Cycle ◽  
Allergic Diseases ◽  
Atopic Disease ◽  
Airway Disease ◽  
Epithelial Barrier ◽  
Metabolic Dysfunction ◽  
New Research

Concomitant dramatic increase in prevalence of allergic and metabolic diseases is part of a modern epidemic afflicting technologically advanced societies. While clinical evidence points to clear associations between various metabolic factors and atopic disease, there is still a very limited understanding of the mechanisms that link the two. Dysregulation of central metabolism in metabolic syndrome, obesity, diabetes, and dyslipidemia has a systemic impact on multiple tissues and organs, including cells of the epithelial barrier. While much of epithelial research in allergy has focused on the immune-driven processes, a growing number of recent studies have begun to elucidate the role of metabolic components of disease. This review will revisit clinical evidence for the relationship between metabolic and allergic diseases, as well as discuss potential mechanisms driving metabolic dysfunction of the epithelial barrier. Among them, novel studies highlight links between dysregulation of the insulin pathway, glucose metabolism, and loss of epithelial differentiation in asthma. Studies of mitochondrial structure and bioenergetics in lean and obese asthmatic phenotypes recently came to light to provide a novel framework linking changes in tricarboxylic acid cycle and oxidative phosphorylation with arginine metabolism and nitric oxide bioavailability. New research established connections between arachidonate metabolism, autophagy, and airway disease, as well as systemic dyslipidemia in atopic dermatitis and ceramide changes in the epidermis. Taken together, studies of metabolism have a great potential to open doors to a new class of therapeutic strategies, better characterization of disease endotypes, as well as enable a systems biology approach to mechanisms of allergic disease.

scholarly journals Astrocytes donate mitochondria to increase glioblastoma tumorigenicity

2021 ◽  
Author(s):  
Justin Lathia ◽  
Dionysios Watson ◽  
Defne Bayik ◽  
Sarah Williford ◽  
Adam Lauko ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cell Communication ◽  
Treatment Resistance ◽  
Extracellular Vesicle ◽  
Host Cells ◽  
Molecular Events ◽  
Mitochondrial Transfer ◽  
New Research

Abstract Glioblastoma (GBM), the most common primary brain cancer in adults1, is characterized by numerous cell-intrinsic/extrinsic interactions that drive tumorigenesis. In addition to cell-surface and secreted protein/extracellular vesicle interactions2,3, treatment resistance of GBM is augmented by the formation of cytoplasmic interconnections and junctions among tumor cells4. These cytoplasmic bridges among tumor cells enable exchange of cellular metabolites as well as mitochondria4, which can play a key role in metabolic function and cellular programming in GBM5,6. However, the contribution of the tumor microenvironment to mitochondrial transfer, as well as the downstream impact of mitochondrial transfer on GBM remains poorly characterized. Here we identified horizontal mitochondrial transfer from the tumor microenvironment as a mechanism that enhances tumorigenesis in glioblastoma. We found that this transfer occurs primarily from brain-resident cells, including astrocytes, and can be appreciated in vitro and in vivo through intercellular connections between GBM cells and non-malignant host cells. The acquisition of astrocyte mitochondria drives an overall enhancement of mitochondrial membrane potential and metabolic capacity, while increasing glioblastoma cell self-renewal and tumor-initiating capacity. Collectively, our findings demonstrate that astrocyte mitochondrial transfer augments the tumorigenic capacity of glioblastoma cells and reveals a previously unknown cell-cell communication mechanism that drives tumor growth. We anticipate our findings will open new research directions to decipher the molecular events linking mitochondria acquisition from non-malignant cells to increased tumorigenicity of recipient GBM cells. This line of research will lead to new therapeutic opportunities targeting this understudied phenomenon and its sequelae in GBM.

scholarly journals Investigation of the mechanism of the neuroprotective effect of the peptide preparation Semax in rat brain under conditions of ischemia-reperfusion

2020 ◽  
pp. 76-78
Author(s):  
О.Ю. Сударкина ◽  
В.Г. Дмитриева ◽  
И.Б. Филиппенков ◽  
В.В. Ставчанский ◽  
А.Е. Денисова ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Cytokines And Chemokines ◽  
Tnf Α ◽  
Ischemic Brain Tissue ◽  
Active Transcription ◽  
Factor C ◽  
Peptide Preparation

Синтетический пептид АКТГ(4-7)PGP ускоряет регресс неврологических нарушений при ишемическом инсульте, однако молекулярные механизмы его действия полностью не известны. На модели полуторачасовой окклюзии средней мозговой артерии крыс был проведен анализ влияния пептида на экспрессию ряда генов и белков, вовлеченных в сигнальные пути, приводящие к воспалению и гибели клеток в условиях ишемии-реперфузии. Показано, что пептид через 24 ч от начала окклюзии снижает повышенный при ишемии уровень экспрессии в ишемизированной ткани мозга крыс мРНК провоспалительных цитокинов и хемокинов IL-1α, IL-1β, IL-6, TNF-α, Cxcl2 и Ccl3. Пептид снижал повышенные при ишемии уровни экспрессии белков металлопротеиназы ММР-9, транскрипционного фактора c-Fos, активных JNK киназ и предотвращал ишемическое снижение уровня активного транскрипционного фактора CREB. The synthetic peptide ACTH (4-7) PGP accelerates the regression of neurological disorders in ischemic stroke, but the molecular mechanisms of its action are not completely known. On the model of an hour and a half occlusion of the rat middle cerebral artery, an analysis was made of the effect of the peptide on the expression of a number of genes and proteins involved in signaling pathways leading to inflammation and cell death under conditions of ischemia-reperfusion. It was shown that the peptide 24 hours after the onset of occlusion reduces the level of expression of mRNA of pro-inflammatory cytokines and chemokines IL-1α, IL-1β, IL-6, TNF-α, Cxcl2 and Ccl3 in ischemic brain tissue. The peptide decreased the levels of expression of proteins metalloproteinase MMP-9, transcription factor c-Fos, active JNK kinases wich were increased under ischemia, and prevented ischemic decrease in the level of active transcription factor CREB.

scholarly journals Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Chen Li ◽  
Yu-Qing Ni ◽  
Hui Xu ◽  
Qun-Yan Xiang ◽  
Yan Zhao ◽  
...  
Keyword(s):  
Human Health ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Cell Communication ◽  
Circular Rnas ◽  
Potential Implication ◽  
Functional Aspects ◽  
Exosomal Mirnas ◽  
Homeostasis Regulation ◽  
Non Coding Rnas

AbstractExosomes play a role as mediators of cell-to-cell communication, thus exhibiting pleiotropic activities to homeostasis regulation. Exosomal non-coding RNAs (ncRNAs), mainly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are closely related to a variety of biological and functional aspects of human health. When the exosomal ncRNAs undergo tissue-specific changes due to diverse internal or external disorders, they can cause tissue dysfunction, aging, and diseases. In this review, we comprehensively discuss the underlying regulatory mechanisms of exosomes in human diseases. In addition, we explore the current knowledge on the roles of exosomal miRNAs, lncRNAs, and circRNAs in human health and diseases, including cancers, metabolic diseases, neurodegenerative diseases, cardiovascular diseases, autoimmune diseases, and infectious diseases, to determine their potential implication in biomarker identification and therapeutic exploration.

scholarly journals Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

2020 ◽  
Vol 21 (6) ◽  
pp. 2252 ◽  
Author(s):  
Tamara Camino ◽  
Lago-Baameiro Nerea ◽  
Bravo Belén ◽  
Sueiro Aurelio ◽  
Couto Iván ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Metabolic Diseases ◽  
Cell Communication ◽  
Cell Of Origin ◽  
Insulin Resistant ◽  
Cell Tissue ◽  
Theoretical Mass ◽  
Adipocyte Cell ◽  
Related Proteins

Extracellular vesicles (EVs) have recently emerged as a relevant way of cell to cell communication, and its analysis has become an indirect approach to assess the cell/tissue of origin status. However, the knowledge about their nature and role on metabolic diseases is still very scarce. We have established an insulin resistant (IR) and two lipid (palmitic/oleic) hypertrophied adipocyte cell models to isolate EVs to perform a protein cargo qualitative and quantitative Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH) analysis by mass spectrometry. Our results show a high proportion of obesity and IR-related proteins in pathological EVs; thus, we propose a panel of potential obese adipose tissue EV-biomarkers. Among those, lipid hypertrophied vesicles are characterized by ceruloplasmin, mimecan, and perilipin 1 adipokines, and those from the IR by the striking presence of the adiposity and IR related transforming growth factor-beta-induced protein ig-h3 (TFGBI). Interestingly, functional assays show that IR and hypertrophied adipocytes induce differentiation/hypertrophy and IR in healthy adipocytes through secreted EVs. Finally, we demonstrate that lipid atrophied adipocytes shed EVs promote macrophage inflammation by stimulating IL-6 and TNFα expression. Thus, we conclude that pathological adipocytes release vesicles containing representative protein cargo of the cell of origin that are able to induce metabolic alterations on healthy cells probably exacerbating the disease once established.

scholarly journals Inferring alterations in cell-to-cell communication in HER2+ breast cancer using secretome profiling of three cell models

2014 ◽  
Vol 111 (9) ◽  
pp. 1853-1863 ◽  
Author(s):  
David J. Klinke ◽  
Yogesh M. Kulkarni ◽  
Yueting Wu ◽  
Christina Byrne-Hoffman
Keyword(s):  
Breast Cancer ◽  
Cell Communication ◽  
Cell Models ◽  
Her2 Breast Cancer ◽  
Secretome Profiling

scholarly journals Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases

2018 ◽  
Vol 19 (8) ◽  
pp. 2208 ◽  
Author(s):  
Yen-Chun Koh ◽  
Guliang Yang ◽  
Ching-Shu Lai ◽  
Monthana Weerawatanakorn ◽  
Min-Hsiung Pan
Keyword(s):  
Disease Progression ◽  
Metabolic Diseases ◽  
Macrophage Polarization ◽  
Colorectal Disease ◽  
New Approach ◽  
Adaptive Immune ◽  
Cytokines And Chemokines ◽  
Preventive Actions ◽  
Pro Inflammatory Cytokines

Macrophages can polarize into two different states (M1 and M2), which play contrasting roles during pathogenesis or tissue damage. M1 polarized macrophages produce pro-inflammatory cytokines and mediators resulting in inflammation, while M2 macrophages have an anti-inflammatory effect. Secretion of appropriate cytokines and chemokines from macrophages can lead to the modification of the microenvironment for bridging innate and adaptive immune responses. Increasing evidence suggests that polarized macrophages are pivotal for disease progression, and the regulation of macrophage polarization may provide a new approach in therapeutic treatment of inflammation-related diseases, including cancer, obesity and metabolic diseases, fibrosis in organs, brain damage and neuron injuries, and colorectal disease. Polarized macrophages affect the microenvironment by secreting cytokines and chemokines while cytokines or mediators that are produced by resident cells or tissues may also influence macrophages behavior. The interplay of macrophages and other cells can affect disease progression, and therefore, understanding the activation of macrophages and the interaction between polarized macrophages and disease progression is imperative prior to taking therapeutic or preventive actions. Manipulation of macrophages can be an entry point for disease improvement, but the mechanism and potential must be understood. In this review, some advanced studies regarding the role of macrophages in different diseases, potential mechanisms involved, and intervention of drugs or phytochemicals, which are effective on macrophage polarization, will be discussed.

Molecular and Epigenetic Basis of Extracellular Vesicles Cell Repair Phenotypes in Targeted Organ-specific Regeneration

2021 ◽  
Vol 21 ◽  
Author(s):  
Ismail Muhamad Fareez ◽  
Wu Yuan Seng ◽  
Ramli Muhammad Zaki ◽  
Aazmi Shafiq ◽  
Ismail Mohamad Izwan
Keyword(s):  
Extracellular Vesicles ◽  
Tissue Regeneration ◽  
Cell Biology ◽  
Metabolic Diseases ◽  
Protein Complexes ◽  
Cell Activity ◽  
Cell Communication ◽  
Stem Cell Activity ◽  
Organ Specific ◽  
Metabolic Unit

: Extracellular vesicles (EVs), which released by most of the cells, constitute a new system of cell-cell communication by transporting DNA, RNA and proteins, in various vesiclesnamely exosomes, apoptotic bodies, protein complexes, high-density lipid (HDL) microvesicles, among others.To ensure accurate regulation of somatic stem cell activity, EVs function as an independent metabolic unit mediating the metabolic homeostasis and pathophysiological of several diseases such as cardiovascular diseases, metabolic diseases, neurodegenerative diseases,immune diseases andcancer. Whist examining the EV biomolecules cargos and its microenvironments that lead to epigenetic alteration of the cell in tissue regeneration, studies have gainedfurther insights into the biogenesis of EVs and their potential roles in cell biology and pathogenicity. Due to its small size, non-virulence, flexibility and ability to cross biological barriers, EVs become promising therapeutic potentials in various diseases.In this review, we describe EV’s mechanism of action in intercellular communication and transfer of biological informationas well as some details about EV-induced epigenetic changes in recipient cells that causephenotypic alteration during tissue regeneration. We also highlight some of the therapeuticpotentials of EVs in organ-specific regeneration.

The transport barrier in intraperitoneal therapy

2005 ◽  
Vol 288 (3) ◽  
pp. F433-F442 ◽  
Author(s):  
Michael F. Flessner
Keyword(s):  
Extracellular Matrix ◽  
Clinical Medicine ◽  
Complex Structure ◽  
Regional Chemotherapy ◽  
Surrounding Tissue ◽  
Transport Barrier ◽  
Physiological Basis ◽  
Cytokines And Chemokines ◽  
Blood Microvessels ◽  
New Research

The peritoneal cavity is important in clinical medicine because of its use as a portal of entry for drugs utilized in regional chemotherapy and as a means of dialysis for anephric patients. The barrier between the therapeutic solution in the cavity and the plasma does not correspond to the classic semipermeable membrane but instead is a complex structure of cells, extracellular matrix, and blood microvessels in the surrounding tissue. New research on the nature of the capillary barrier and on the orderly array of extracellular matrix molecules has provided insights into the physiological basis of osmosis and the alterations in transport that result from infusion of large volumes of fluid. The anatomic peritoneum is highly permeable to water, small solutes, and proteins and therefore is not a physical barrier. However, the cells of the mesothelium play an essential role in the immune response in the cavity and produce cytokines and chemokines in response to contact with noncompatible solutions. The process of inflammation, which depends on the interaction of mesothelial, interstitial, and endothelial cells, ultimately leads to angiogenesis and fibrosis and the functional alteration of the barrier. New animal models, such as the transgenic mouse, will accelerate the discovery of methods to preserve the functional peritoneal barrier.

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