Project description:To explore the key genes involved in spontaneous diabetic cardiomyopathy, db/db and BKS mice were used to examine the differently expressed genes in the related progresses. Briely, the heart transcriptome of db/db and BKS mice was correlated with the heart function, cardiomyocyte ultrastructure and histopathology characters.
Project description:Diabetes mellitus (DM) causes the change in the components of the plasma, which may induce tissue and organ injuries, including the heart and kidney. In the diabetic model db/db mice, intravenous injection of purified dipeptidyl peptidase III (DPPIII) attenuated the heart and kidney damages provoked by DM without alteration in blood glucose level. This led us to hypothesize that there might be peptide(s) that are involved in the progression of the DM-mediated damages and are cleaved by DPPIII. To explore the peptides, the whole peptidomics analysis was conducted using tandem mass spectrometry, in which peptides derived from the plasma of PBS-infused C57BL/6 mice, PBS-infused db/db mice, and DPPIII-treated db/db mice were compared. All of the lists of the peptides in the three mouse groups were shown in the raw data formatted and excel files.
Project description:Diabetes mellitus (DM) causes the change in the components of the plasma, which may induce tissue and organ injuries, including the heart and kidney. In the diabetic model db/db mice, intravenous injection of purified dipeptidyl peptidase III (DPPIII) attenuated the heart and kidney damages provoked by DM without alteration in blood glucose level. This led us to hypothesize that there might be peptide(s) that are involved in the progression of the DM-mediated damages and are cleaved by DPPIII. To explore the peptides, the whole peptidomics analysis (shotgun peptidomics) was conducted using tandem mass spectrometry, in which peptides derived from the plasma of PBS-infused C57BL/6 mice, PBS-infused db/db mice, and DPPIII-treated db/db mice were compared. The raw mass spectrometry data were deposited to the ProteomeXchange with the dataset identifier PXD025440. Together with the mass spectrometry analysis and other experiments, we identified a peptide named Peptide 2 (AA sequence: RLLWENGNL) as a substrate of DPPIII. Peptide 2 is a part of C3f (53% identical), and C3f can act as an anaphylatoxin like C3a. To quantify the amount in plasma derived from the plasma of PBS-infused C57BL/6 mice, PBS-infused db/db mice, and DPPIII-treated db/db mice, selected reaction monitoring (SRM) assay was performed. All of the chromatograms and quantified data obtained by SRM from the three mouse groups were shown in the Analyst formated and PDF files.
Project description:The type 2 diabetes medication, rosiglitazone, has come under scrutiny for possibly increasing the risk of cardiac disease and death. To investigate the effects of rosiglitazone on the diabetic heart, we performed cardiac transcriptional profiling of a murine model of type 2 diabetes, the C57BL/KLS-leprdb/leprdb (db/db) mouse. We compared cardiac gene expression profiles from three groups: untreated db/db mice (db-c), db/db mice after rosiglitazone treatment (db-t), and non-diabetic db/+ mice. Mice were divided into three groups: Non-diabetic controls (db/+), untreated diabetic controls (db-c), and rosiglitazone-treated diabetic mice (db-t). Whole-heart RNA from five mice from each of the three groups after four months with or without treatment was used for microarray analysis.Universal Reference RNAs for mouse (Stratagene, La Jolla, CA) were purchased as microarray reference controls.
Project description:The type 2 diabetes medication, rosiglitazone, has come under scrutiny for possibly increasing the risk of cardiac disease and death. To investigate the effects of rosiglitazone on the diabetic heart, we performed cardiac transcriptional profiling of a murine model of type 2 diabetes, the C57BL/KLS-leprdb/leprdb (db/db) mouse. We compared cardiac gene expression profiles from three groups: untreated db/db mice (db-c), db/db mice after rosiglitazone treatment (db-t), and non-diabetic db/+ mice.
Project description:This research was detected the differentially expressed circular RNAs in the heart tissues of WT mouse and db/db mouse. We have completed the circRNA Arraystar mouse V.2 analysis of the 3 wt mouse and 3 db/db mouse age 3 month. Whole heart tissue RNA samples were collected and then were digested with RNAse R. Total RNA from each sample was quantified using the NanoDrop ND-1000. The sample preparation and microarray hybridization were performed based on the Arraystar?s standard protocols.
Project description:To explore the unique pathogenesis of DCM and analyzed the differences in gene expression, associated pathways and immune cell infiltration among different organs that are targeted by high glucose by bioinformatics-based strategy. In order to find the specific factors that trigger DCM, we contrasted the gene profile of DCM to that of other diabetic diseases including diabetic peripheral neuropathy (DPN) and nephropathy (DN). we performed RNA-seq and miRNA sequencing on heart tissue from db/db mice to explore the transcriptome alterations in DCM pathogenesis including lncRNA, miRNA and mRNA.
Project description:Macrophage dysfunction and polarization plays key role in chronic inflammation associated with diabetes and its complications. However, the effect of diabetes on macrophage transcriptome including long non-coding RNAs is not known. Here, we analyzed global changes in transcriptome of bone marrow macrophages isolated from type 2 diabetic db/db mice and control littermates db/+ mice using high throughput RNA-seq technique. Data analysis showed that expression of genes relevant to fibrosis, cell adhesion and inflammation were altered in diabetic db/db mice relative to control db/+ mice. Furthermore, expression of several known and novel long non coding RNAs and nearby genes was altered in db/db mice. Gene ontology and IPA showed activation of signaling netwroks relevant to fibrosis, cell adhesion and inflammatory pathways . This study for the first time demonstrated that diabetes profoundly affects macrophage transcriptome including expression of long non coding RNAs and altered the levels of genes relevant to diabetes complications.
Project description:The majority of diabetics are susceptible to cardiac dysfunction and heart failure, while conventional drug therapy cannot correct diabetic cardiomyopathy (DCM) progression. Herein, we assessed the potential role and therapeutic value of ubiquitin-specific protease 28 (USP28) on the metabolic vulnerability of DCM. PPARα-/- in the db/db background mice were constructed to check the mechanism of USP28 in vivo. Inducible cardiac-specific deletion of Mfn2 in the db/db background mice was utilized to evaluate USP28-mediated cardioprotection. chromatin immunoprecipitation (ChIP) assays revealed that PPARα promote mitofusin 2 (Mfn2) transcription, thereby impeding mitochondrial morphofunctional defects.
Project description:Macrophage dysfunction and polarization plays key role in chronic inflammation associated with diabetes and its complications. However, the effect of diabetes on macrophage transcriptome including long non-coding RNAs is not known. Here, we analyzed global changes in transcriptome of bone marrow macrophages isolated from type 2 diabetic db/db mice and control littermates db/+ mice using high throughput RNA-seq technique. Data analysis showed that expression of genes relevant to fibrosis, cell adhesion and inflammation were altered in diabetic db/db mice relative to control db/+ mice. Furthermore, expression of several known and novel long non coding RNAs and nearby genes was altered in db/db mice. Gene ontology and IPA showed activation of signaling netwroks relevant to fibrosis, cell adhesion and inflammatory pathways . This study for the first time demonstrated that diabetes profoundly affects macrophage transcriptome including expression of long non coding RNAs and altered the levels of genes relevant to diabetes complications. Bone marrow macrophages were isolated from 12 weeks old type 2 diabetic male db/db mice and control littermates db/+ mice. These were differentiated in culture for 7-8 days in the presence of 10 ng/ml of MCSF-1 (BMMC) or 20 ng/ml of GM-CSF (BMGM). Then RNA was extracted and used for RNA-seq.