Dataset Information

Temporal Expression Profiling of Plasma Proteins in Type 1 Diabetes Progression

ABSTRACT: A longitudinal proteomic profiling of human plasma using TMT-10plex-based LC-MS/MS analysis was performed to track temporal proteomic changes of T1D patients (n = 11) across 9 serial time points, spanning the period of T1D natural progression, in comparison with those of the matching healthy controls (n = 10). Longitudinal expression profiles of >2000 human plasma proteins in T1D natural progression were presented in the current study.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Type 1 Diabetes Mellitus

SUBMITTER: Qibin Zhang

LAB HEAD: Qibin Zhang

PROVIDER: PXD007884 | Pride | 2018-03-08

REPOSITORIES: Pride

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Publications

Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression.

Liu Chih-Wei CW Bramer Lisa L Webb-Robertson Bobbie-Jo BJ Waugh Kathleen K Rewers Marian J MJ Zhang Qibin Q

Journal of proteomics 20171007

Blood markers other than islet autoantibodies are greatly needed to indicate the pancreatic beta cell destruction process as early as possible, and more accurately reflect the progression of Type 1 Diabetes Mellitus (T1D). To this end, a longitudinal proteomic profiling of human plasma using TMT-10plex-based LC-MS/MS analysis was performed to track temporal proteomic changes of T1D patients (n=11) across 9 serial time points, spanning the period of T1D natural progression, in comparison with tho ...[more]

PMID: 28993202

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Project description:The retention of a nucleus in the mature state of fish red blood cells (RBCs), and the ability to easily collect and manipulate blood in non-terminal experiments, makes it an ideal tissue on which to study the cellular stress response in fish. Through the use of the cGRASP 16K salmonid microarray, we are currently investigating differences in RBC global gene transcription in fish held under control conditions (12C) and exposed to heat stress (one hour at 25C followed by recovery at 12C). Repeated blood sampling (via a dorsal aorta cannula) enables us to examine the individual stress response over time. Samples were taken pre-heat stress (representing individual control) and at 4 and 24 hours post heat stress (representing early and late transcriptional regulation). A total of ~3000 features had significant signal when hybridized with RBC RNA derived targets and cannulation did not have a significant effect on RBC mRNA expression at the investigated time points. Genes involved in the stress response, immune response, and apoptosis were among those showing the highest dysregulation during both early and late transcriptional regulation. Additionally, genes related to the differentiation and development of blood cells were upregulated at the twenty-four hour time point. This study enables a broader understanding of the mechanisms underpinning the stress response in fish and the discovery of novel genes that are regulated in a stress specific manner. Moreover, salmonid transcripts that are consistently dysregulated in blood in response to heat stress are potential candidates of non-lethal biomarkers of exposure to this particular stressor. Two condition experiment, control (11C) and heat stressed fish (one hour at 25C followed by return to 11C). Six fish in each treatment. 3 repeated samples taken from each individual at time 0, 4 hours post heat stress and 24 hours. Common reference design used, with all experimental samples (control or heat stress) combined with reference pool RBC RNA on each array.

Project description:Human type 1 diabetes (T1D) arises through autoimmunity towards the insulin-producing pancreatic β cells and is modeled by the BioBreeding (BB) rat. Factors associated with islet autoimmunity are dilute and difficult to directly measure in the periphery. Therefore, we previously utilized microarray-based bioassay where human T1D sera were used to induce a disease-specific gene expression signature in unrelated, healthy peripheral blood mononuclear cells (PBMC). Here we report that sera of both spontaneously diabetic BB DRlyp/lyp and diabetes inducible BB DR+/+ rats induce inflammatory signatures in healthy PBMC of non-diabetic Brown Norway (BN) rats, while allogeneic BN sera does not. Consistent with their common T1D susceptibility, transcriptional signatures of both BB sub-strains share identity, including cytokines, immune receptors and signaling molecules. However, like the human T1D signature, the DRlyp/lyp signature, which is associated with progression to diabetes, is differentiated from that of the DR+/+ by induction of many IL-1 regulated genes. Addition of IL-1RA to cultures significantly ablates the DRlyp/lyp signature. Daily treatment of DRlyp/lyp rats with human recombinant IL-1RA significantly delays onset and sera of treated animals do not induce the characteristic IL-1 signature. Consistent with the presence of immune regulation in DR+/+ rats is induction of a signature showing negative regulation of the NFκB pathway. This study supports prior human investigations of serum that reflect disease processes associated with progression to T1D and add to a growing body of evidence implicating the balance of IL-1 and IL-1RA as key factors influencing the severity and outcome of inflammatory responses. Experiment Overall Design: The induction of gene expression was accomplished by culturing the PBMCs of healthy day180 BN donor rats for 6 h at 37°C in 5% CO2 with a) 20% autologous BN plasma(10 replicates), b) allogeneic BN plasma (15 replicates), c) allogeneic DRlyp/lyp plasma (day 60, 4 replicates), or d) DR+/+ plasma (day 60, 4 replicates). Healthy BN PBMCs were also cultured with d60 DRlyp/lyp serum supplemented with IL-1RA (4 replicates) as well as autologous BN serum supplemented with IL-1B (4 replicates), to respectively block or induce IL-1 mediated gene expression. To determine if IL-1RA-treatment of DRlyp/lyp rats would result in modulation of the DRlyp/lyp signature, additional DRlyp/lyp rats were treated with hIL-1RA (n=6) or PBS (n=6). Rats were treated for 10 days, beginning at d30, then serum was collected at d40 and used to induce gene expression in PBMCs isolated from healthy d180 BN rats. Thus, there are a total of 53 chips being the addition of all the sample conditions mentioned above.

Dataset Information

Temporal Expression Profiling of Plasma Proteins in Type 1 Diabetes Progression

Publications

Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression.

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