Proteomic and transcriptomic profiling reveal different aspects of aging in the kidney.
Ontology highlight
ABSTRACT:
SUBMITTER: Takemon Y
PROVIDER: S-EPMC8096428 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The kidney is an excellent model for studying organ aging. Kidney function shows steady decline with age and is easy to assay using urine or blood samples. However, little is known about the molecular changes that take place in the kidney during the aging process. In order to better understand the molecular changes that occur with age, we measured mRNA and protein levels in 188 genetically diverse mice at ages 6, 12, and 18 months. We observed distinctive change in mRNA and protein levels as a function of age. Changes in both mRNA and protein are associated with increased immune infiltration and decreases in mitochondrial function. Proteins show a greater extent of change and reveal changes in a wide array of biological processes including unique, organ-specific features of aging in kidney. Most importantly, we observed functionally important age-related changes in protein that occur in the absence of corresponding changes in mRNA. Our findings suggest that mRNA profiling alone provides an incomplete picture of molecular aging in the kidney and that examination of changes in proteins is essential to understand aging processes that are not transcriptionally regulated.
2021-03-11 | PXD023823 | Pride
Project description:(1) Background: Aging is associated with a progressive decline in muscle mass and function. Aging is also a primary risk factor for metabolic syndrome, which further alters muscle metabolism. However, the molecular mechanisms involved remain to be clarified. Herein we performed omic profiling to decipher in muscle which dominating processes are associated with healthy aging and metabolic syndrome in old men. (2) Methods: This study included 15 healthy young, 15 healthy old, and 9 old men with metabolic syndrome. Old men were selected from a well-characterized cohort, and each vastus lateralis biopsy was used to combine global transcriptomic and proteomic analyses. (3) Results: Over-representation analysis of differentially expressed genes (ORA) and functional class scoring of pathways (FCS) indicated that healthy aging was mainly associated with upregulations of apoptosis and immune function and downregulations of glycolysis and protein catabolism. ORA and FCS indicated that with metabolic syndrome the dominating biological processes were upregulation of proteolysis and downregulation of oxidative phosphorylation. Proteomic profiling matched 586 muscle proteins between individuals. The proteome of healthy aging revealed modifications consistent with a fast-to-slow transition and downregulation of glycolysis. These transitions were reduced with metabolic syndrome, which was more associated with alterations in NADH/NAD+ shuttle and β-oxidation. Proteomic profiling further showed that all old muscles overexpressed protein chaperones to preserve proteostasis and myofiber integrity. There was also evidence of aging-related increases in reactive oxygen species but better detoxifications of cytotoxic aldehydes and membrane protection in healthy than in metabolic syndrome muscles. (4) Conclusions: Most candidate proteins and mRNAs identified herein constitute putative muscle biomarkers of healthy aging and metabolic syndrome in old men.
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Project description:BackgroundActivation of microglia and astrocytes, a prominent hallmark of both aging and Alzheimer's disease (AD), has been suggested to contribute to aging and AD progression, but the underlying cellular and molecular mechanisms are largely unknown.MethodsWe performed RNA-seq analyses on microglia and astrocytes freshly isolated from wild-type and APP-PS1 (AD) mouse brains at five time points to elucidate their age-related gene-expression profiles.ResultsOur results showed that from 4 months onward, a set of age-related genes in microglia and astrocytes exhibited consistent upregulation or downregulation (termed "age-up"/"age-down" genes) relative to their expression at the young-adult stage (2 months). And most age-up genes were more highly expressed in AD mice at the same time points. Bioinformatic analyses revealed that the age-up genes in microglia were associated with the inflammatory response, whereas these genes in astrocytes included widely recognized AD risk genes, genes associated with synaptic transmission or elimination, and peptidase-inhibitor genes.ConclusionsOverall, our RNA-seq data provide a valuable resource for future investigations into the roles of microglia and astrocytes in aging- and amyloid-β-induced AD pathologies.
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Project description:Diabetic retinopathy (DR) and diabetic kidney disease (DKD) are complications of diabetes and place serious health and economic burdens on society. However, the identification and characterization of early biomarkers for DKD, especially for nonproliferative DR (NPDR) patients with DKD, are still needed. This study aimed to demonstrate the plasma proteomic profiles of NPDR+DKD and NPDR patients and identify potential biomarkers for early diagnosis of DKD. Fifteen plasma samples from the NPDR group and nine from the NPDR+DKD group were analyzed by LC-MS/MS to identify the differentially expressed proteins between the two groups. Functional enrichment, protein-protein interaction and clinical feature correlation analyses revealed the target protein candidates, which were verified using ELISA and receiver operating characteristic (ROC) analysis. In total, 410 proteins were detected in plasma; 15 were significantly upregulated and 7 were downregulated in the NPDR+DKD group. Bioinformatics analysis suggested that DKD is closely related to cell adhesion and immunity pathways. β-2-Microglobulin (B2M) and vimentin (VIM) were upregulated in NPDR+DKD, enriched as hub proteins and strongly correlated with clinical features. ELISA showed that B2M (p<0.001) and VIM (p<0.0001) were significantly upregulated in NPDR+DKD compared with NPDR. In ROC analysis, B2M and VIM could distinguish DKD from NPDR with area under the curve values of 0.9000 (p < 0.0001) and 0.9950. Our proteomic study revealed alterations in the proteomic profile and identified VIM and B2M as early biomarkers of DKD, laying the foundation for the prevention, diagnosis and treatment of DKD.
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Project description:Forage plays a critical role in the milk production of dairy cows; however, the mechanisms regulating bovine milk synthesis in dairy cows fed high forage rations with different basal forage types are not well-understood. In the study, rice straw (RS, low-quality) and alfalfa hay (AH, high-quality) diets were fed to lactating cows to explore how forage quality affected the molecular mechanisms regulating milk production using RNA-seq transcriptomic method with iTRAQ proteomic technique. A total of 554 transcripts (423 increased and 131 decreased) and 517 proteins (231 up-regulated and 286 down-regulated) were differentially expressed in the mammary glands of the two groups. The correlation analysis demonstrated seven proteins (six up-regulated and one down-regulated) had consistent mRNA expression. Functional analysis of the differentially expressed transcripts/proteins suggested that enhanced capacity for energy and fatty acid metabolism, increased protein degradation, reduced protein synthesis, decreased amino acid metabolism and depressed cell growth were related to RS consumption. The results indicated cows consuming RS diets may have had depressed milk protein synthesis because these animals had decreased capacity for protein synthesis, enhanced proteolysis, inefficient energy generation and reduced cell growth. Additional work evaluating RS- and AH-based rations may help better isolate molecular adaptations to low nutrient availability during lactation.
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Project description:BackgroundWaterlogging is one of the most serious abiotic stresses affecting wheat-growing regions in China. Considerable differences in waterlogging tolerance have been found among different wheat varieties, and the mechanisms governing the waterlogging tolerance of wheat seeds during germination have not been elucidated.ResultsThe results showed no significant difference between the germination rate of 'Bainong 207' (BN207) (after 72 h of waterlogging treatment) and that of the control seeds. However, the degree of emulsification and the degradation rate of endosperm cells under waterlogging stress were higher than those obtained with the control treatment, and the number of amyloplasts in the endosperm was significantly reduced by waterlogging. Transcriptomic data were obtained from seed samples (a total of 18 samples) of three wheat varieties, 'Zhoumai 22' (ZM22), BN207 and 'Bainong 607' (BN607), subjected to the waterlogging and control treatments. A comprehensive analysis identified a total of 2775 differentially expressed genes (DEGs). In addition, an analysis of the correlations among the expression difference levels of DEGs and the seed germination rates of the three wheat varieties under waterlogging stress revealed that the relative expression levels of 563 and 398 genes were positively and negatively correlated with the germination rate of the wheat seeds, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the difference in the waterlogging tolerance among the three wheat varieties was related to the abundance of key genes involved in the glycolysis pathway, the starch and sucrose metabolism pathway, and the lactose metabolism pathway. The alcohol dehydrogenase (ADH) gene in the endosperm of BN607 was induced immediately after short-term waterlogging, and the energy provided by the glycolysis pathway enabled the BN607 seeds to germinate as early as possible; in addition, the expression of the AP2/ERF transcription factor was upregulated to further enhance the waterlogging tolerance of this cultivar.ConclusionsTaken together, the results of this study help elucidate the mechanisms through which different wheat varieties respond to waterlogging stress during germination.
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Project description:PurposeMetastatic breast cancer (MBC) is not curable and there is a growing interest in personalized therapy options. Here we report molecular profiling of MBC focusing on molecular evolution in actionable alterations.Experimental designSixty-two patients with MBC were included. An analysis of DNA, RNA, and functional proteomics was done, and matched primary and metastatic tumors were compared when feasible.ResultsTargeted exome sequencing of 41 tumors identified common alterations in TP53 (21; 51%) and PIK3CA (20; 49%), as well as alterations in several emerging biomarkers such as NF1 mutations/deletions (6; 15%), PTEN mutations (4; 10%), and ARID1A mutations/deletions (6; 15%). Among 27 hormone receptor-positive patients, we identified MDM2 amplifications (3; 11%), FGFR1 amplifications (5; 19%), ATM mutations (2; 7%), and ESR1 mutations (4; 15%). In 10 patients with matched primary and metastatic tumors that underwent targeted exome sequencing, discordances in actionable alterations were common, including NF1 loss in 3 patients, loss of PIK3CA mutation in 1 patient, and acquired ESR1 mutations in 3 patients. RNA sequencing in matched samples confirmed loss of NF1 expression with genomic NF1 loss. Among 33 patients with matched primary and metastatic samples that underwent RNA profiling, 14 actionable genes were differentially expressed, including antibody-drug conjugate targets LIV-1 and B7-H3.ConclusionsMolecular profiling in MBC reveals multiple common as well as less frequent but potentially actionable alterations. Genomic and transcriptional profiling demonstrates intertumoral heterogeneity and potential evolution of actionable targets with tumor progression. Further work is needed to optimize testing and integrated analysis for treatment selection.
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Project description:Ovarian aging precedes that of any other mammalian organ and is the primary cause of female age-related infertility. The biological mechanisms responsible for ovarian aging remain unclear. Previous studies have been limited by their use of bulk RNA-sequencing, which masks the dynamic and heterogeneous nature of the ovary. In this study, we spatially resolved the transcriptomic landscape of ovaries from young and aged outbred mice. In total, we defined eight main ovarian cell populations, all of which were characterized by significant transcriptomic changes between young and aged samples. Further sub-cluster analysis revealed separate transcriptomes for distinct granulosa cell populations found in young versus aged mice, in addition to an oocyte sub-cluster population completely absent from aged mouse ovaries. This study provides a new perspective on mammalian ovarian aging using spatial transcriptomics to achieve deeper understanding of the localization and cell-population-specific mechanisms underlying age-related fertility decline.
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Project description:Plant growth and development are regulated by a tightly controlled interplay between cell division, cell expansion and cell differentiation during the entire plant life cycle from seed germination to maturity and seed propagation. To explore some of the underlying molecular mechanisms in more detail, we selected different aerial tissue types of the model plant Arabidopsis thaliana, namely rosette leaf, flower and silique/seed and performed proteomic, phosphoproteomic and transcriptomic analyses of sequential growth stages using tandem mass tag-based mass spectrometry and RNA sequencing. With this exploratory multi-omics dataset, development dynamics of photosynthetic tissues can be investigated from different angles. As expected, we found progressive global expression changes between growth stages for all three omics types and often but not always corresponding expression patterns for individual genes on transcript, protein and phosphorylation site level. The biggest difference between proteomic- and transcriptomic-based expression information could be observed for seed samples. Proteomic and transcriptomic data is available via ProteomeXchange and ArrayExpress with the respective identifiers PXD018814 and E-MTAB-7978.
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