scholarly journals Proteomics to Metabolomics: A New Insight Into the Pathogenesis of Hypertensive Nephropathy

2021 ◽  
Author(s):  
Yasin Eshraghi ◽  
Maryam Abedi ◽  
Yousof Gheisari
Keyword(s):  
Expression Profiles ◽  
Principal Component ◽  
Kidney Cortex ◽  
Hypertensive Nephropathy ◽  
Renal Disorder ◽  
Leading Role ◽  
Underlying Mechanisms ◽  
Novel Therapeutic Strategies ◽  
Protein Expression Profiles ◽  
End Stage

Abstract Background Hypertensive nephropathy (HN) is a high burden disorder and a leading cause of end-stage renal disorder. In spite of huge investigations, the underlying mechanisms are yet largely unknown. Systems biology is a promising approach to provide a comprehensive insight towards this complex disorder. Methods Protein expression profiles of kidney tubule and cortex sub-compartments were retrieved from the PRIDE database and the quality of the datasets were assessed using principal component analysis (PCA) and hierarchical clustering. Differentially expressed proteins (DEPs) were detected and their attributed metabolites were enriched and their interactions were assessed in multi-layer networks. Moreover, considering the DEPs and the predicted metabolites, key biomedical phenomena with a leading role in HN pathogenesis were proposed. Results Amino acid and purine metabolisms are the most prominent alteration in kidney cortex whereas dysregulation of energy hemostasis is a key pathogenic mechanism in tubule. Besides, actin cytoskeleton disorganization is an enriched pathway in both anatomical areas. Conclusion The proteomics profiles of kidney sub-compartments were analyzed using a top-down approach to infer the main pathogenic processes. The constructed holistic map of HN can be exploited to propose novel therapeutic strategies.

scholarly journals Ppia is the most stable housekeeping gene for qRT-PCR normalization in kidney tissues of Pkd1 deficient mouse models

2021 ◽  
Author(s):  
Juan J Muñoz ◽  
Ana C Anauate ◽  
Andressa G Amaral ◽  
Frederico M Ferreira ◽  
Elieser H Watanabe ◽  
...  
Keyword(s):  
Mouse Models ◽  
Expression Profiles ◽  
Housekeeping Genes ◽  
Housekeeping Gene ◽  
Renal Disorder ◽  
Ideal Number ◽  
Autosomal Dominant Polycystic Kidney ◽  
Suitable Reference ◽  
Stage Renal Disease ◽  
End Stage

Abstract Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited renal disorder, characterized by renal cyst development leading to end-stage renal disease. Although the appropriate choice of suitable reference is critical for quantitative RNA analysis, no comparison of frequently used “housekeeping” genes is available. Here, we determined the validity of 7 candidate housekeeping genes (Actb, Actg1, B2m, Gapdh, Hprt, Pgam1 and Ppia) in kidney tissues from mouse models orthologous to ADPKD, including a cystic mice (CY) 10–12 weeks old (Pkd1flox/flox:Nestincre/Pkd1flox/-:Nestincre, n = 10) and non-cystic (NC) controls (Pkd1flox/flox/Pkd1flox/-, n = 10), Pkd1-haploinsufficient (HT) mice (Pkd1+/-, n = 6) and wild-type (WT) controls (Pkd1+/+, n = 6) and a severely cystic (SC) mice 15 days old (Pkd1V/V, n = 7) and their controls (CO, n = 5). Gene expression data were analyzed using six distinct statistical softwares. The estimation of the ideal number of genes suggested the use of Ppia alone as sufficient, although not ideal, to analyze groups altogether. Actb, Hprt and Ppia expression profiles were correlated in all samples. Ppia was identified as the most stable housekeeping gene, while Gapdh was the least stable for all kidney samples. Stat3 expression level was consistent with upregulation in SC compared to CO when normalized by Ppia expression. In conclusion, present findings identified Ppia as the best housekeeping gene for CY + NC and SC + CO groups, while Hprt was the best for the HT + WT group.

scholarly journals Ppia is the most stable housekeeping gene for qRT-PCR normalization in kidneys of three Pkd1-deficient mouse models

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juan J. Muñoz ◽  
Ana C. Anauate ◽  
Andressa G. Amaral ◽  
Frederico M. Ferreira ◽  
Elieser H. Watanabe ◽  
...  
Keyword(s):  
Mouse Models ◽  
Expression Profiles ◽  
Housekeeping Genes ◽  
Housekeeping Gene ◽  
Renal Disorder ◽  
Ideal Number ◽  
Autosomal Dominant Polycystic Kidney ◽  
Suitable Reference ◽  
Stage Renal Disease ◽  
End Stage

AbstractAutosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited renal disorder, characterized by renal cyst development leading to end-stage renal disease. Although the appropriate choice of suitable reference is critical for quantitative RNA analysis, no comparison of frequently used “housekeeping” genes is available. Here, we determined the validity of 7 candidate housekeeping genes (Actb, Actg1, B2m, Gapdh, Hprt, Pgam1 and Ppia) in kidney tissues from mouse models orthologous to ADPKD, including a cystic mice (CY) 10–12 weeks old (Pkd1flox/flox:Nestincre/Pkd1flox/−:Nestincre, n = 10) and non-cystic (NC) controls (Pkd1flox/flox/Pkd1flox/-, n = 10), Pkd1-haploinsufficient (HT) mice (Pkd1+/−, n = 6) and wild-type (WT) controls (Pkd1+/+, n = 6) and a severely cystic (SC) mice 15 days old (Pkd1V/V, n = 7) and their controls (CO, n = 5). Gene expression data were analyzed using six distinct statistical softwares. The estimation of the ideal number of genes suggested the use of Ppia alone as sufficient, although not ideal, to analyze groups altogether. Actb, Hprt and Ppia expression profiles were correlated in all samples. Ppia was identified as the most stable housekeeping gene, while Gapdh was the least stable for all kidney samples. Stat3 expression level was consistent with upregulation in SC compared to CO when normalized by Ppia expression. In conclusion, present findings identified Ppia as the best housekeeping gene for CY + NC and SC + CO groups, while Hprt was the best for the HT + WT group.

scholarly journals From the Molecular Mechanism to Pre-clinical Results: Anti-epileptic Effects of Fingolimod

2020 ◽  
Vol 18 (11) ◽  
pp. 1126-1137 ◽  
Author(s):  
Yam Nath Paudel ◽  
Efthalia Angelopoulou ◽  
Christina Piperi ◽  
Vadym Gnatkovsky ◽  
Iekhsan Othman ◽  
...  
Keyword(s):  
Symptomatic Relief ◽  
Drug Repurposing ◽  
Clinical Results ◽  
Regulatory Compliance ◽  
Health Concern ◽  
Sphingosine 1 Phosphate ◽  
Underlying Mechanisms ◽  
Novel Therapeutic Strategies ◽  
Experimental Findings ◽  
End Stage

: Epilepsy is a devastating neurological condition characterized by long-term tendency to generate unprovoked seizures, affecting around 1-2 % of the population worldwide. Epilepsy is a serious health concern which often associates with other neurobehavioral comorbidities that further worsen disease conditions. Despite tremendous research, the mainstream anti-epileptic drugs (AEDs) exert only symptomatic relief leading to 30% of untreatable patients. This reflects the complexity of the disease pathogenesis and urges the precise understanding of underlying mechanisms in order to explore novel therapeutic strategies that might alter the disease progression as well as minimize the epilepsy-associated comorbidities. Unfortunately, the development of novel AEDs might be a difficult process engaging huge funds, tremendous scientific efforts and stringent regulatory compliance with a possible chance of end-stage drug failure. Hence, an alternate strategy is drug repurposing, where anti-epileptic effects are elicited from drugs that are already used to treat non-epileptic disorders. : Herein, we provide evidence of the anti-epileptic effects of Fingolimod (FTY720), a modulator of sphingosine-1-phosphate (S1P) receptor, USFDA approved already for Relapsing-Remitting Multiple Sclerosis (RRMS). Emerging experimental findings suggest that Fingolimod treatment exerts disease-modifying anti-epileptic effects based on its anti-neuroinflammatory properties, potent neuroprotection, anti-gliotic effects, myelin protection, reduction of mTOR signaling pathway and activation of microglia and astrocytes. We further discuss the underlying molecular crosstalk associated with the anti-epileptic effects of Fingolimod and provide evidence for repurposing Fingolimod to overcome the limitations of current AEDs.

A Comparative Proteomic Analysis of Platelets from Healthy Human Patients and Chronic ITP Patients Receiving AMG 531, a Thrombopoiesis-Stimulating Protein.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1313-1313 ◽  
Author(s):  
John M. Sloan ◽  
John P. Coburn ◽  
Amy M. Bertino ◽  
Valerie Wood ◽  
David J. Kuter
Keyword(s):  
Protein Expression ◽  
Expression Profiles ◽  
Protein Detection ◽  
Principal Component ◽  
Healthy Human ◽  
Two Dimensional Gel Electrophoresis ◽  
Chronic Itp ◽  
Platelet Protein ◽  
Platelet Disorder ◽  
Protein Expression Profiles

Abstract AMG 531 is a novel thrombopoiesis-stimulating “peptibody” consisting of an Fc carrier domain linked to 4 identical peptides that bind to and activate Mpl, the human thrombopoietin receptor. It has proven efficacy in raising platelet counts of patients with chronic ITP, and is being evaluated in chemotherapy-induced thrombocytopenia and myelodysplastic syndrome. While platelets from healthy subjects receiving AMG 531 reportedly behave normally in platelet aggregation studies, the effects of this medication on protein expression profiles are not known. The platelets from 12 healthy patients without known platelet defects and 9 chronic ITP patients receiving AMG 531 were isolated and their proteins extracted. Proteins with isoelectric points between pH 3 and 7 were separated by two-dimensional gel electrophoresis and stained with Sypro protein detection reagent. These gels were scanned and compared using Progenesis SameSpots software. In this pH range, there were approximately 5000 unique spots detected, representing individual proteins, isoforms of proteins or cleavage products. On multivariate analysis, approximately 11% of these proteins were expressed at levels significantly different between healthy patients without a known platelet disorder and chronic ITP patients receiving AMG 531. Principal component analysis substantiates these differences and a protein dendrogram has been created. The most significant protein expression differences are identified by tandem mass spectrometry. It is not known if these differences in protein expression represent younger platelets, stimulation of protein synthesis by AMG 531, or altered platelet protein expression as a reflection of the ITP. There is no known clinical correlate of these protein changes.

scholarly journals Discovery of Biomarkers for Osteosarcoma by Proteomics Approaches

Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Yoshiyuki Suehara ◽  
Daisuke Kubota ◽  
Kazutaka Kikuta ◽  
Kazuo Kaneko ◽  
Akira Kawai ◽  
...  
Keyword(s):  
Protein Expression ◽  
Therapeutic Response ◽  
Expression Profiles ◽  
Tumor Biology ◽  
Malignant Bone Tumors ◽  
Two Dimensional Gel Electrophoresis ◽  
New Information ◽  
Expression Studies ◽  
Novel Therapeutic Strategies ◽  
Protein Expression Profiles

Osteosarcomas are the most common malignant bone tumors, and the identification of useful tumor biomarkers and target proteins is required to predict the clinical outcome of patients and therapeutic response as well as to develop novel therapeutic strategies. Global protein expression studies, namely, proteomic studies, can offer important clues to understanding the tumor biology that cannot be obtained by other approaches. These studies, such as two-dimensional gel electrophoresis and mass spectrometry, have provided protein expression profiles of osteosarcoma that can be used to develop novel diagnostic and therapeutic biomarkers, as well as to understand biology of tumor progression and malignancy. In this paper, a brief description of the methodology will be provided followed by a few examples of the recent proteomic studies that have generated new information regarding osteosarcomas.

scholarly journals Evaluation of dihydropteridine reductase activities in patients with kidney failure

Pteridines ◽  
2013 ◽  
Vol 24 (3) ◽  
pp. 219-223
Author(s):  
Şaziye Sezin Palabıyık ◽  
Ali Aşçı ◽  
Gözde Girgin ◽  
Gönül Şahin ◽  
Ramazan Çetinkaya ◽  
...  
Keyword(s):  
Kidney Failure ◽  
Diabetic Control ◽  
Control Group ◽  
Dihydropteridine Reductase ◽  
Hypertensive Nephropathy ◽  
Waste Products ◽  
Renal Disorder ◽  
Healthy Control ◽  
Stage Renal Disease ◽  
End Stage

AbstractEnd-stage renal disease (ESRD) is the inability of the kidneys to remove waste products from the blood. The most important factors causing ESRD that require hemodialysis are diabetes and hypertension. There are limited numbers of studies to evaluate tetrahydrobiopterin pathway in these patients. The aim of the study was to evaluate tetrahydrobiopterin pathway by measuring its important components, biopterin to creatinine concentrations and dihydropteridine reductase activities in diabetes and hypertension patients treated with/without hemodialysis. The patients undergoing hemodialysis were classified as diabetic nephropathy (n=21), hypertensive nephropathy (n=20) and others (n=30), while the controls consisted of healthy subjects (n=21), diabetic subjects (n=23) and hypertensive subjects (n=22) without any renal disorder. It was found that urinary biopterin to creatinine concentrations significantly increased in kidney failure patients undergoing hemodialysis compared to the healthy control group (p<0.05). Additionally, there were significant differences in urinary biopterin to creatinine concentrations between diabetes or hypertension patients and their hypertensive or diabetic control counterparts (both p<0.05). Our results indicated an alteration in tetrahydrobiopterin pathway in ESRD, and in the presence of secondary pathologies such as diabetes and hypertension in the patients undergoing hemodialysis, more considerable changes are observed in the pathway.

Could Antioxidant Supplementation Delay Progression of Cardiovascular Disease in End-Stage Renal Disease Patients?

2020 ◽  
Vol 19 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Stefanos Roumeliotis ◽  
Athanasios Roumeliotis ◽  
Xenia Gorny ◽  
Peter R. Mertens
Keyword(s):  
Oxidative Stress ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Close Association ◽  
Omega 3 ◽  
Endstage Renal Disease ◽  
Increased Risk ◽  
Underlying Mechanisms ◽  
Stage Renal Disease ◽  
End Stage

In end-stage renal disease patients, the leading causes of mortality are of cardiovascular (CV) origin. The underlying mechanisms are complex, given that sudden heart failure is more common than acute myocardial infarction. A contributing role of oxidative stress is postulated, which is increased even at early stages of chronic kidney disease, is gradually augmented in parallel to progression to endstage renal disease and is further accelerated by renal replacement therapy. Oxidative stress ensues when there is an imbalance between reactive pro-oxidants and physiologically occurring electron donating antioxidant defence systems. During the last decade, a close association of oxidative stress with accelerated atherosclerosis and increased risk for CV and all-cause mortality has been established. Lipid peroxidation has been identified as a trigger for endothelial dysfunction, the first step towards atherogenesis. In order to counteract the deleterious effects of free radicals and thereby ameliorate, or delay, CV disease, exogenous administration of antioxidants has been proposed. Here, we attempt to summarize existing data from studies that test antioxidants for CV protection, such as vitamins E and C, statins, omega-3 fatty acids and N-acetylcysteine.

scholarly journals Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agents

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Alieh Gholaminejad ◽  
Yousof Gheisari ◽  
Sedigheh Jalali ◽  
Amir Roointan
Keyword(s):  
Iga Nephropathy ◽  
Regulatory Network ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Signature ◽  
Gene Expression Omnibus ◽  
Integrative Approach ◽  
Potential Factors ◽  
Ngf Signaling ◽  
Underlying Mechanisms

Abstract Background IgA nephropathy (IgAN) is a kidney disease recognized by the presence of IgA antibody depositions in kidneys. The underlying mechanisms of this complicated disease are remained to be explored and still, there is an urgent need for the discovery of noninvasive biomarkers for its diagnosis. In this investigation, an integrative approach was applied to mRNA and miRNA expression profiles in PBMCs to discover a gene signature and novel potential targets/biomarkers in IgAN. Methods Datasets were selected from gene expression omnibus database. After quality control checking, two datasets were analyzed by Limma to identify differentially expressed genes/miRNAs (DEGs and DEmiRs). Following identification of DEmiR-target genes and data integration, intersecting mRNAs were subjected to different bioinformatic analyses. The intersecting mRNAs, DEmiRs, related transcription factors (from TRRUST database), and long-non coding RNAs (from LncTarD database) were used for the construction of a multilayer regulatory network via Cytoscape. Result “GSE25590” (miRNA) and “GSE73953” (mRNA) datasets were analyzed and after integration, 628 intersecting mRNAs were identified. The mRNAs were mainly associated with “Innate immune system”, “Apoptosis”, as well as “NGF signaling” pathways. A multilayer regulatory network was constructed and several hub-DEGs (Tp53, STAT3, Jun, etc.), DEmiRs (miR-124, let-7b, etc.), TFs (NF-kB, etc.), and lncRNAs (HOTAIR, etc.) were introduced as potential factors in the pathogenesis of IgAN. Conclusion Integration of two different expression datasets and construction of a multilayer regulatory network not only provided a deeper insight into the pathogenesis of IgAN, but also introduced several key molecules as potential therapeutic target/non-invasive biomarkers.

Adipokines and Gut Hormones in End-Stage Renal Disease

2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 298-302
Author(s):  
Robert H. Mak ◽  
Wai Cheung
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Peptide Yy ◽  
Gut Hormones ◽  
Poor Quality ◽  
Mortality And Morbidity ◽  
Novel Therapeutic Strategies ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

Cachexia is common in end-stage renal disease (ESRD) patients, and it is an important risk factor for poor quality of life and increased mortality and morbidity. Chronic inflammation is an important cause of cachexia in ESRD patients. In the present review, we examine recent evidence suggesting that adipokines or adipocytokines such as leptin, adiponectin, resistin, tumor necrosis factor α, interleukin-6, and interleukin-1β may play important roles in uremic cachexia. We also review the physiology and the potential roles of gut hormones, including ghrelin, peptide YY, and cholecystokinin in ESRD. Understanding the molecular pathophysiology of these novel hormones in ESRD may lead to novel therapeutic strategies.

scholarly journals Comprehensive Comparison of Amnion Stromal Cells and Chorion Stromal Cells by RNA-Seq

2021 ◽  
Vol 22 (4) ◽  
pp. 1901
Author(s):  
Brielle Jones ◽  
Chaoyang Li ◽  
Min Sung Park ◽  
Anne Lerch ◽  
Vimal Jacob ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stromal Cells ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Principal Component ◽  
Differentially Expressed ◽  
Inflammatory Factor ◽  
Next Generation Sequencing Technology ◽  
Angiogenic Potential ◽  
Anti Inflammatory

Mesenchymal stromal cells derived from the fetal placenta, composed of an amnion membrane, chorion membrane, and umbilical cord, have emerged as promising sources for regenerative medicine. Here, we used next-generation sequencing technology to comprehensively compare amniotic stromal cells (ASCs) with chorionic stromal cells (CSCs) at the molecular and signaling levels. Principal component analysis showed a clear dichotomy of gene expression profiles between ASCs and CSCs. Unsupervised hierarchical clustering confirmed that the biological repeats of ASCs and CSCs were able to respectively group together. Supervised analysis identified differentially expressed genes, such as LMO3, HOXA11, and HOXA13, and differentially expressed isoforms, such as CXCL6 and HGF. Gene Ontology (GO) analysis showed that the GO terms of the extracellular matrix, angiogenesis, and cell adhesion were significantly enriched in CSCs. We further explored the factors associated with inflammation and angiogenesis using a multiplex assay. In comparison with ASCs, CSCs secreted higher levels of angiogenic factors, including angiogenin, VEGFA, HGF, and bFGF. The results of a tube formation assay proved that CSCs exhibited a strong angiogenic function. However, ASCs secreted two-fold more of an anti-inflammatory factor, TSG-6, than CSCs. In conclusion, our study demonstrated the differential gene expression patterns between ASCs and CSCs. CSCs have superior angiogenic potential, whereas ASCs exhibit increased anti-inflammatory properties.

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