Multi-modal analysis of Col1a1-GFP in vitro vs in vivo state
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE198185 | GEO | 2022/03/12
REPOSITORIES: GEO
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Project description:Multi-modal analysis of Col1a1-GFP in vitro vs in vivo state
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Project description:Background: Heart failure (HF) has been recognized as global pandemic with a high rate of associated hospitalization, morbidity and mortality. Although numerous advances have been made, its representative molecular signatures remain largely unknown, especially the role of genes in HF progression. The aim of the present prospective follow-up study was to reveal potential biomarkers associated with the progression of heart failure. Methods: We collected left ventricular heart tissue from 21 HF patients and 9 healthy donors as study cohort and generated multi-level transcriptomic data. By using Masson staining to calculate the fibrosis percentage for each sample, we applied lasso regression model to identify the genes associated with fibrosis as well as progression. The genes were further validated by immunohistochemistry (IHC) staining in the same cohort and qRT-PCR using another independent cohort (20 HF and 9 healthy donors). Enzyme linked immunosorbent assay (ELISA) was used to measure the plasma level in validation cohort (87 HF patients) for predicting HF progression. Results: Based on the multi-level transcriptomic data, we examined differentially expressed genes [mRNAs, microRNAs, and long non-coding RNAs (lncRNAs)] in study cohort. The follow-up functional annotations and regulatory network reveal their potential roles in regulating extracellular matrix. We further identified several genes that were associated with fibrosis. By using the survival time before transplantation, COL1A1 was identified as a potential biomarker for HF progression and its up-regulation was confirmed by both IHC and qRT-PCR. Furthermore, COL1A1 content >281.7 ng/ml in plasma was found to be associated with poor survival within one year of heart transplantation from heart failure [Hazard Ratio (HR): 27.52, 95% Confidence Interval (CI): 7.474 to 101.3, Log-rank p-value<1.0×10-4]. Conclusions: Our results suggested that COL1A1 is a plasma biomarker of HF and associated with HF progression, especially to predict the 1-year survival from HF onset to transplantation.
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Project description:Multi-level transcriptome sequencing identifies COL1A1 as a candidate marker in human heart failure progression
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Project description:A) Whole lung tissue from 24 months (n=7) and 3 months old (n=8) mice was dissociated and single-cell mRNAseq libraries generated with Drop-Seq. B) Bulk RNA-seq data was generated from whole mouse lung tissue of old (n=3) and young (n=3) samples. C) Bulk RNA-seq data was generated from flow-sorted macrophages from old (n=7) and young (n=5) mice and flow-sorted epithelial cells from old (n=4) and young (n=4) mice.
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Project description:Dermatofibrosarcoma protuberans (DFSP) is an aggressive spindle cell neoplasm. It is associated with the chromosomal translocation, t(17:22), which fuses the COL1A1 and PDGFbeta genes. We determined the characteristic gene expression profile of DFSP and characterized DNA copy number changes in DFSP by array-based comparative genomic hybridization (array CGH). Fresh frozen and formalin-fixed, paraffin-embedded samples of DFSP were analyzed by array CGH (four cases) and DNA microarray analysis of global gene expression (nine cases). The nine DFSPs were readily distinguished from 27 other diverse soft tissue tumors based on their gene expression patterns. Genes characteristically expressed in the DFSPs included PDGFbeta and its receptor, PDGFRB, APOD, MEOX1, PLA2R, and PRKCA. Array CGH of DNA extracted either from frozen tumor samples or from paraffin blocks yielded equivalent results. Large areas of chromosomes 17q and 22q, bounded by COL1A1 and PDGFbeta, respectively, were amplified in DFSP. Expression of genes in the amplified regions was significantly elevated. Our data shows that: 1) DFSP has a distinctive gene expression profile; 2) array CGH can be applied successfully to frozen or formalin-fixed, paraffin-embedded tumor samples; 3) a characteristic amplification of sequences from chromosomes 17q and 22q, demarcated by the COL1A1 and PDGFbeta genes, respectively, was associated with elevated expression of the amplified genes.
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Project description:Diabetes mellitus (DM) and related complications continue to exert a significant burden on health care systems globally. Although conventional pharmacological therapies are beneficial in the management of this metabolic condition, it is still necessary to seek novel potential molecules for its management. On this basis, we have synthesised and evaluated the anti-diabetic properties of four novel thiazolidinedione (TZD)-derivatives. The TZD derivatives were synthesised through the pharmacophore hybridisation strategy based on N-arylpyrrole and TZD. The resultant derivatives at different concentrations were screened against key enzymes of glucose metabolism and glucose utilisation in the liver (HEP-G2) cell line. Additionally, peroxisome proliferator-activated receptor-γ activation was performed through docking studies. Docking of these molecules against PPAR-γ predicted strong binding, similar to that of rosiglitazone. Hence, TZDD2 was able to increase glucose uptake in the liver cells as compared to the control. The enzymatic inhibition assays showed a relative inhibition activity; with all four derivatives exhibiting ≥ 50% inhibition activity in the α-amylase inhibition assay and a concentration dependent activity in the α-glucosidase inhibition assay. All four derivatives exhibited ≥30% inhibition in the aldose reductase inhibition assay, except TZDD1 at 10 µg/mL. Interestingly, TZDD3 showed a decreasing inhibition activity. In the dipeptidyl peptidase-4 inhibition assay, TZDD2 and TZDD4 exhibited ≥20% inhibition activity.
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