γENaC/CD9 in urinary extracellular vesicles as a potential biomarker of MR activity

2021 ◽  
Author(s):  
Tomoaki Hayakawa ◽  
Atsunori Fukuhara ◽  
Aya Saiki ◽  
Michio Otsuki ◽  
Iichiro Shimomura
Keyword(s):  
Correlation Coefficient ◽  
Extracellular Vesicles ◽  
Protein Level ◽  
Cell Types ◽  
Organ Damage ◽  
Plasma Aldosterone Concentration ◽  
Protein Levels ◽  
Sodium Transporters ◽  
Potential Biomarker ◽  
Multiple Cell

Primary aldosteronism (PA) is caused by autonomous overproduction of aldosterone, which induces organ damage directly via activation of the mineralocorticoid receptor (MR); however, no specific or sensitive biomarkers are able to reflect MR activity. Recently, it is found that urinary extracellular vesicles (uEVs) are secreted by multiple cell types in the kidney and are an enriched source of kidney-specific proteins. Here, we evaluate sodium transporters in uEVs as candidates of biomarkers of MR activity in the clinical setting. Sixteen patients were examined to determine their plasma aldosterone concentration (PAC) and renin activity, and their morning urine was collected. The protein levels of two sodium transporters in uEVs, γ-epithelial sodium channel (γENaC) and thiazide-sensitive sodium chloride cotransporter (NCC), were quantified by Western blot analysis, and their clinical correlation with PAC was determined. Consequently, we found PAC was significantly correlated with the γENaC protein level adjusted by the CD9 protein level in uEVs (correlation coefficient = 0.71). PAC was also correlated with the NCC protein level adjusted by the CD9 protein level in uEVs (correlation coefficient = 0.61). In two PA patients, treatment with an MR antagonist or adrenalectomy reduced γENaC/CD9 in uEVs. In conclusion, γENaC/CD9 in uEVs is a valuable biomarker of MR activity in PA patients and may be a useful biomarker for other MR-associated diseases.

scholarly journals Emerging role of extracellular vesicles in liver diseases

2019 ◽  
Vol 317 (5) ◽  
pp. G739-G749 ◽  
Author(s):  
Harmeet Malhi
Keyword(s):  
Extracellular Vesicles ◽  
Cell Communication ◽  
Cell Types ◽  
Cell Responses ◽  
Therapeutic Delivery ◽  
Disease States ◽  
Therapeutic Uses ◽  
Potential Biomarker ◽  
Secretion Pathways

Extracellular vesicles (EVs) are membrane-defined nanoparticles released by most cell types. The EVs released by cells may differ quantitatively and qualitatively from physiological states to disease states. There are several unique properties of EVs, including their proteins, lipids and nucleic acid cargoes, stability in circulation, and presence in biofluids, which make them a critical vector for cell-to-cell communication and impart utility as a biomarker. EVs may also serve as a vehicle for selective cargo secretion. Similarly, EV cargo may be selectively manipulated for targeted therapeutic delivery. In this review an overview is provided on the EV classification, biogenesis, and secretion pathways, which are conserved across cell types. Next, cargo characterization and effector cell responses are discussed in the context of nonalcoholic steatohepatitis, alcoholic hepatitis, and acetaminophen-induced liver injury. The review also discusses the potential biomarker and therapeutic uses of circulating EVs.

scholarly journals Therapeutic Potential of Extracellular Vesicles in Hypertension-Associated Kidney Disease

Hypertension ◽  
2021 ◽  
Vol 77 (1) ◽  
pp. 28-38
Author(s):  
Olga Martinez-Arroyo ◽  
Ana Ortega ◽  
Josep Redon ◽  
Raquel Cortes
Keyword(s):  
Kidney Disease ◽  
Extracellular Vesicles ◽  
Renal Damage ◽  
Therapeutic Potential ◽  
Cell Communication ◽  
Cell Types ◽  
Organ Damage ◽  
Renal Diseases ◽  
Biological Processes ◽  
Potential Use

Hypertension-mediated organ damage frequently includes renal function decline in which several mechanisms are involved. The present review outlines the state of the art on extracellular vesicles in hypertension and hypertension-related renal damage. Emerging evidence indicates that extracellular vesicles, small vesicles secreted by most cell types and body fluids, are involved in cell-to-cell communication and are key players mediating biological processes such as inflammation, endothelial dysfunction or fibrosis, mechanisms present the onset and progression of hypertension-associated kidney disease. We address the potential use of extracellular vesicles as markers of hypertension-mediated kidney damage severity and their application as therapeutic agents in hypertension-associated renal damage. The capacity of exosomes to deliver a wide variety of cargos to the target cell efficiently makes them a potential drug delivery system for treatment of renal diseases.

Update on the role of Angiogenesis in Diabetes associated Nephropathy

2021 ◽  
pp. 3947-3954
Author(s):  
Munish Kakkar ◽  
Shreeja Singh ◽  
Tapan Behl ◽  
Sukhbir Singh ◽  
Neelam Sharma ◽  
...  
Keyword(s):  
Renal Failure ◽  
Diabetic Nephropathy ◽  
Morphological Changes ◽  
Cell Types ◽  
Organ Damage ◽  
Lethal Complications ◽  
Multiple Cell ◽  
Original Size ◽  
Predictable Condition

Diabetic mellitus is common worldwide health problem which brings about different rigorous complications like retinopathy, nephropathy and numerous other lethal complications. Diabetic nephropathy is the major cause for blindness and renal failure in many of the developing countries. Hyperglycemia induced diabetic nephropathy gets elicited through improved development of reactive oxygen species in multiple cell types. The starting of organ damage or kidney failure shows some symptomatic effect or morphological changes as in one or both the kidneys like expansion or enlargement of kidneys from their original size and this enlargement process is known as nephromegaly. Microalbuminuria is the best possible predictable condition proceeding towards renal failure. This review briefly discussed about the diabetic nephropathy with regard to progression, angiogenic and non-angiogenic factors involved in pathogenesis and treatment of angiogenesis in diabetic nephropathy.

scholarly journals Extracellular Vesicles in CNS Developmental Disorders

2020 ◽  
Vol 21 (24) ◽  
pp. 9428
Author(s):  
Ana Rita Gomes ◽  
Nasim Bahram Sangani ◽  
Tiago G. Fernandes ◽  
M. Margarida Diogo ◽  
Leopold M. G. Curfs ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Developmental Disorders ◽  
Complex Structure ◽  
Cell Types ◽  
The Body ◽  
Neural Cells ◽  
Cytoplasmic Proteins ◽  
Gene And Protein Expression ◽  
Multiple Cell ◽  
And Function

The central nervous system (CNS) is the most complex structure in the body, consisting of multiple cell types with distinct morphology and function. Development of the neuronal circuit and its function rely on a continuous crosstalk between neurons and non-neural cells. It has been widely accepted that extracellular vesicles (EVs), mainly exosomes, are effective entities responsible for intercellular CNS communication. They contain membrane and cytoplasmic proteins, lipids, non-coding RNAs, microRNAs and mRNAs. Their cargo modulates gene and protein expression in recipient cells. Several lines of evidence indicate that EVs play a role in modifying signal transduction with subsequent physiological changes in neurogenesis, gliogenesis, synaptogenesis and network circuit formation and activity, as well as synaptic pruning and myelination. Several studies demonstrate that neural and non-neural EVs play an important role in physiological and pathological neurodevelopment. The present review discusses the role of EVs in various neurodevelopmental disorders and the prospects of using EVs as disease biomarkers and therapeutics.

scholarly journals Reduction of serotonin receptor 2A protein level in peripheral blood lymphocytes during antipsychotic medication is biomarker of therapy safety

2020 ◽  
pp. 58-59
Author(s):  
А.М. Заботина ◽  
М.Н. Грунина ◽  
Е.В. Волкова ◽  
Р.Ф. Насырова ◽  
А.Е. Тараскина
Keyword(s):  
Peripheral Blood ◽  
Protein Level ◽  
Serotonin Receptor ◽  
Mrna Level ◽  
Peripheral Blood Lymphocytes ◽  
Antipsychotic Therapy ◽  
Blood Lymphocytes ◽  
Protein Levels ◽  
Potential Biomarker ◽  
Serotonin Receptor 2A

В лимфоцитах периферической крови (ЛПК) в группе пациентов с коморбидным течением шизофрении с синдромом алкогольной зависимости показаны более низкие значения количества белка рецептора 5-НТ2А и уровня его мРНК по сравнению с группой с неотягощенной психической патологией (р<0.001). Безопасная фармакотерапия ассоциирована со снижением количества рецептора 5-НТ2А в ЛПК на 28-й день без изменения уровня транскрипции гена, возможно вызванного интернализацией рецептора. We studied mRNA and protein levels of serotonin receptor 2A (5-НТ2А) in lymphocytes of schizophrenia patients both before and after 28 days of antipsychotic therapy in order to estimate biomarkers of efficacy and safety of the treatment. We found lower mRNA and protein levels of 5-НТ2А in peripheral blood lymphocytes (PBL) of schizophrenia patients with alcohol addiction syndrome than in PBL of schizophrenia patients without addictions (р<0.001). Absence of common adverse side effects (antipsychotic-induced weight gain, parkinsonism, akathisia) during antipsychotic therapy was associated with reduction of 5-НТ2А protein level in PBL by 28th day of the treatment, while HTR2A mRNA level was not changed. Reduction of 5-НТ2А protein level in PBL by 28th day may be a potential biomarker of the antipsychotic therapy safety.

scholarly journals Curcumin-primed human BMSC-derived extracellular vesicles reverse IL-1β-induced catabolic responses of OA chondrocytes by upregulating miR-126-3p

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shushan Li ◽  
Sabine Stöckl ◽  
Christoph Lukas ◽  
Marietta Herrmann ◽  
Christoph Brochhausen ◽  
...  
Keyword(s):  
Gene Expression ◽  
P38 Mapk ◽  
Extracellular Vesicles ◽  
Caspase 3 ◽  
Cell Types ◽  
Potential Candidate ◽  
Catabolic Genes ◽  
Multiple Cell ◽  
And Migration ◽  
And Control

Abstract Background Curcumin has anti-inflammatory effects and qualifies as a potential candidate for the treatment of osteoarthritis (OA). However, curcumin has limited bioavailability. Extracellular vesicles (EVs) are released by multiple cell types and act as molecule carrier during intercellular communication. We assume that EVs can maintain bioavailability and stability of curcumin after encapsulation. Here, we evaluated modulatory effects of curcumin-primed human (h)BMSC-derived EVs (Cur-EVs) on IL-1β stimulated human osteoarthritic chondrocytes (OA-CH). Methods CellTiter-Blue Viability- (CTB), Caspase 3/7-, and live/dead assays were used to determine range of cytotoxic curcumin concentrations for hBMSC and OA-CH. Cur-EVs and control EVs were harvested from cell culture supernatants of hBMSC by ultracentrifugation. Western blotting (WB), transmission electron microscopy, and nanoparticle tracking analysis were performed to characterize the EVs. The intracellular incorporation of EVs derived from PHK26 labeled and curcumin-primed or control hBMSC was tested by adding the labeled EVs to OA-CH cultures. OA-CH were pre-stimulated with IL-1β, followed by Cur-EV and control EV treatment for 24 h and subsequent analysis of viability, apoptosis, and migration (scratch assay). Relative expression of selected anabolic and catabolic genes was assessed with qRT-PCR. Furthermore, WB was performed to evaluate phosphorylation of Erk1/2, PI3K/Akt, and p38MAPK in OA-CH. The effect of hsa-miR-126-3p expression on IL-1β-induced OA-CH was determined using CTB-, Caspase 3/7-, live/dead assays, and WB. Results Cur-EVs promoted viability and reduced apoptosis of IL-1β-stimulated OA-CH and attenuated IL-1β-induced inhibition of migration. Furthermore, Cur-EVs increased gene expression of BCL2, ACAN, SOX9, and COL2A1 and decreased gene expression of IL1B, IL6, MMP13, and COL10A1 in IL-1β-stimulated OA-CH. In addition, phosphorylation of Erk1/2, PI3K/Akt, and p38 MAPK, induced by IL-1β, is prevented by Cur-EVs. Cur-EVs increased IL-1β-reduced expression of hsa-miR-126-3p and hsa-miR-126-3p mimic reversed the effects of IL-1β. Conclusion Cur-EVs alleviated IL-1β-induced catabolic effects on OA-CH by promoting viability and migration, reducing apoptosis and phosphorylation of Erk1/2, PI3K/Akt, and p38 MAPK thereby modulating pro-inflammatory signaling pathways. Treatment of OA-CH with Cur-EVs is followed by upregulation of expression of hsa-miR-126-3p which is involved in modulation of anabolic response of OA-CH. EVs may be considered as promising drug delivery vehicles of curcumin helping to alleviate OA.

scholarly journals An Update on Novel Therapeutic Warfronts of Extracellular Vesicles (EVs) in Cancer Treatment: Where We Are Standing Right Now and Where to Go in the Future

2019 ◽  
Vol 2019 ◽  
pp. 1-21 ◽  
Author(s):  
Muhammad Babar Khawar ◽  
Muddasir Hassan Abbasi ◽  
Zerwa Siddique ◽  
Amin Arif ◽  
Nadeem Sheikh
Keyword(s):  
Drug Delivery ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Clinical Applications ◽  
Pathological Conditions ◽  
Potential Biomarker ◽  
Wide Range ◽  
Intercellular Communications ◽  
Multiple Stages ◽  
Novel Therapeutic

Extracellular vesicles (EVs) are a heterogeneous group of membrane-bounded vesicles that are believed to be produced and secreted by presumably all cell types under physiological and pathological conditions, including tumors. EVs are very important vehicles in intercellular communications for both shorter and longer distances and are able to deliver a wide range of cargos including proteins, lipids, and various species of nucleic acids effectively. EVs have been emerging as a novel biotherapeutic platform to efficiently deliver therapeutic cargos to treat a broad range of diseases including cancer. This vast potential of drug delivery lies in their abilities to carry a variety of cargos and their ease in crossing the biological membranes. Similarly, their presence in a variety of body fluids makes them a potential biomarker for early diagnosis, prognostication, and surveillance of cancer. Here, we discuss the relatively least and understudied aspects of EV biology and tried to highlight the obstacles and limitations in their clinical applications and also described most of the new warfronts to beat cancer at multiple stages. However, much more challenges still remain to evaluate EV-based therapeutics, and we are very much hopeful that the current work prompts further discovery.

scholarly journals A miRNA signature in endothelial cell-derived extracellular vesicles in tumor-bearing mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
James V. McCann ◽  
Amber Liu ◽  
Luca Musante ◽  
Uta Erdbrügger ◽  
Joanne Lannigan ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Vascular Dysfunction ◽  
Expression Patterns ◽  
Immune Surveillance ◽  
Cell Types ◽  
Lineage Tracing ◽  
Diagnostic Tools ◽  
Tumor Bearing ◽  
Multiple Cell ◽  
Cell Type Specific

AbstractExtracellular vesicles (EVs) play important roles in tumor progression by altering immune surveillance, promoting vascular dysfunction, and priming distant sites for organotropic metastases. The miRNA expression patterns in circulating EVs are important diagnostic tools in cancer. However, multiple cell types within the tumor microenvironment (TME) including cancer cells and stromal cells (e.g. immune cells, fibroblasts, and endothelial cells, ECs) contribute to the pool of circulating EVs. Because EVs of different cellular origins have different functional properties, auditing the cargo derived from cell type-specific EVs in the TME is essential. Here, we demonstrate that a murine EC lineage-tracing model (Cdh5-CreERT2:ZSGreenl/s/l mice) can be used to isolate EC-derived extracellular vesicles (EC-EVs). We further show that purified ZSGreen+ EVs express expected EV markers, they are transferable to multiple recipient cells, and circulating EC-EVs from tumor-bearing mice harbor elevated levels of specific miRNAs (e.g. miR-30c, miR-126, miR-146a, and miR-125b) compared to non tumor-bearing counterparts. These results suggest that, in the tumor setting, ECs may systemically direct the function of heterotypic cell types either in the circulation or in different organ micro-environments via the cargo contained within their EVs.

scholarly journals Microbe-Host Communication by Small RNAs in Extracellular Vesicles: Vehicles for Transkingdom RNA Transportation

2019 ◽  
Vol 20 (6) ◽  
pp. 1487 ◽  
Author(s):  
Heon-Jin Lee
Keyword(s):  
Extracellular Vesicles ◽  
Small Rnas ◽  
Cell Communication ◽  
Cell Types ◽  
Eukaryotic Cells ◽  
Biological Research ◽  
Interspecies Communication ◽  
Microbe Interactions ◽  
Multiple Cell ◽  
Host Microbe Interactions

Extracellular vesicles (EVs) are evolutionary well-conserved nano-sized membranous vesicles that are secreted by both prokaryotic and eukaryotic cells. Recently, they have gained great attention for their proposed roles in cell-to-cell communication, and as biomarkers for human disease. In particular, small RNAs (sRNAs) contained within EVs have been considered as candidate interspecies-communication molecules, due to their demonstrated capacity to modulate gene expression in multiple cell types and species. While research into this field is in its infancy, elucidating the mechanisms that underlie host–microbe interactions and communications promises to impact many fields of biological research, including human health and medicine. Thus, this review discussed the results of recent studies that have examined the ways in which EVs and sRNAs mediate ‘microbe–host’ and ‘host–microbe’ interspecies communication.

scholarly journals A multi-centre study of neutrophil-to-lymphocyte ratio in primary aldosteronism

2020 ◽  
Author(s):  
Renata Libianto ◽  
Jinbo Hu ◽  
Min R Chee ◽  
Jesse Hoo ◽  
Yin Y Lim ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Cell Types ◽  
Organ Damage ◽  
Receptor Activation ◽  
Neutrophil To Lymphocyte Ratio ◽  
Multi Centre Study ◽  
Peripheral Tissues ◽  
Lymphocyte Ratio ◽  
Markers Of Inflammation ◽  
Potential Biomarker

Abstract Background Hypertensive patients with primary aldosteronism (PA) have a higher risk of cardiovascular complications than those with blood pressure-matched essential hypertension. The excess cardiovascular consequences of PA can be attributed to the pro-inflammatory effect of excessive aldosterone and mineralocorticoid receptor activation in a range of peripheral tissues and cell types. The neutrophil-to-lymphocyte ratio (NLR) is a widely available markers of inflammation which has been shown to predict cardiovascular outcome in the general population. This study aims to evaluate the use of NLR as a potential biomarker of PA and PA severity. Methods Patients with PA (n=355) were identified from two large PA databases in Australia and China, while controls (n=222) were patients with hypertension who were referred for assessment but did not meet the diagnostic criteria for PA. The NLR was retrospectively collected from routine full blood examination, prior to commencement of targeted treatment for PA. Results The NLR did not differ between PA patients and hypertensive controls (median 2.3 and 2.4, p=0.563). However, amongst patients with PA, the NLR was positively correlated with baseline and post-saline aldosterone levels (r=0.22 and p&lt;0.001 for both) and negatively correlated with serum potassium (r=-0.15, p=0.006). Furthermore, in a logistic regression analysis of data from patients with PA, the NLR predicted the presence of co-morbid CKD (defined as eGFR &lt; 60mL/min/1.73m 2) with an odds ratio of 1.5 (p=0.003). Conclusion Whilst the NLR did not distinguish PA from controls, it was a marker of PA severity, being associated with aldosterone concentration as well as the presence of CKD. A prospective study is needed to further clarify the role of NLR in predicting end-organ damage associated with PA.

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