Project description:Dipeptidyl peptidase-4 (Dpp4) inhibitors are used worldwide to combat diabetes, however, their roles in cardiovascular disorders are yet to be defined. Here we show that a DPP4 inhibitor, linagliptin, contributes for the suppression of capillary rarefaction in cardiac tissues of dietary obese mice model. Imposing a high fat diet into mice induced capillary rarefaction and cardiac dysfunction. These pathologies associated with high DPP4 level in circulation, and the administration of linagliptin into dietary obese mice suppressed the development of capillary rarefaction and ameliorated cardiac dysfunction. Early growth response protein 1 (EGR1), known as an angiogenic transcription factor, is significantly reduced in the cardiac tissue upon metabolic stress, and this suppression was inhibited by the administration of linagliptin.
Project description:Effect of expression of dipeptidyl peptidase-IV (DPP-IV) in U373 cell line on uncontrolled cell proliferation and aberrant interactions with the brain extracellular matrix.
Project description:Tubulointerstitial injury plays an important role in diabetic nephropathy (DN) progression; however, no reliable urinary molecule has been used to predict tubulointerstitial injury and renal outcome of DN clinically. In this study, based on tubulointerstitial transcriptome, we identified secretory leukocyte peptidase inhibitor (SLPI) as the molecule associated with renal fibrosis and prognosis of DN. In tubular cells, high glucose could upregulate SLPI, which bound with β-catenin and GSK-3β reciprocally, abolished the interaction between β-catenin and GSK-3β, diminished GSK-3β-regulated β-catenin phosphorylation and the subsequent ubiquitination and degradation, thus led to β-catenin signaling activation and renal fibrosis. Db/db mice injected with adenovirus carrying Slpi-3xflag-GFP (Ad-Slpi-GFP) developed β-catenin signaling activation in the proximal tubule, worse albuminuria and tubulointerstitial fibrosis. Conversely, Slpi knockout (KO) mice with STZ-induced DN developed less albuminuria, tubulointerstitial fibrosis and β-catenin signaling activation. Furthermore, clinical studies showed that urinary SLPI protein level (uSLPI/Cr) had significant correlation with intrarenal SLPI mRNA and interstitial fibrosis. In an independent prospective cohort enrolled 711 patients with biopsy proven DN, uSLPI/Cr level was significantly associated with eGFR slope and improved the prediction value of renal outcome. Together, our study identified SLPI as a novel critical regulator for the progression of tubulointerstitial injury, which may be used as an independent risk predictor of DN progression.
Project description:Signal peptide peptidase (SPP) plays an essential role in among all eukaryotes. The knock out lines of A. thaliana SPP (AtSPP) is lethal and the substrates of AtSPP are not identified. Based on the situation, we constructed the plants with AtSPP over-expressed and knock down to investigate the role of AtSPP. We also used the data to find the candidate substrates of AtSPP, which regulates intermembrane proteolysis, would have crucial physiological functions as well as control the gene expression encoding the substrates.
Project description:We report that the PRC1 component polycomb group ring finger 6 (Pcgf6) is required to maintain embryonic stem cell (ESC) identity. In contrast to canonical PRC1, Pcgf6 acts as a positive regulator of transcription and binds predominantly to promoters bearing active chromatin marks. Pcgf6 is expressed at high levels in ESCs, and knockdown reduces the expression of the core ESC regulators Oct4,Sox2, and Nanog. Conversely, Pcgf6 overexpression prevents downregulation of these factors and impairs differentiation. In addition, Pcgf6 enhanced reprogramming in both mouse and human somatic cells. The genomic binding profile of Pcgf6 is highly similar to that of trithorax group proteins, but not of PRC1 or PRC2 complexes, suggesting that Pcgf6 functions atypically in ESCs. Our data reveal novel roles for Pcgf6 in directly regulating Oct4, Nanog, Sox2, and Lin28 expression to maintain ESC identity. To identify Pcgf6-bound genomic DNA regions in mouse embryonic stem cells, we fixed mouse ESCs and isolated Pcgf6-bound genomic DNA regions for deep sequencing analysis.
Project description:Auto Immune REgulator (AIRE) protein expression in HEK293 cells Three cell-lines where used in the study: HEK293-NC; control cell-line expressing yellow fluorescent protein (YFP) HEK-AIRE1, HEK-AIRE2; two different clone-derived Autoimmune regulator protein expressing cell-lines HEK-AIRE-D312A; cell line expressing Autoimmune regulator protein with D312A mutation in the first PHD finger With all cell-lines three independent experiments were performed.
Project description:Analysis of our transcriptome and RNA immunoprecipitation experiments indicate DND1 acts as a positive regulator of chromatin modifiers in male germ cells, linking RNA binding proteins and epigenetic regulation.
Project description:Helicobacter pylori, a pathogenic member of phylum Campylobacterota (formerly Epsilonproteobacteria), is recognized as the leading cause of several human gastric pathologies, including acute and chronic gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In the last two decades, the alarming increase of the antibiotic resistance levels to first-line and even “rescue” antibiotics, especially clarithromycin, metronidazole and levofloxacin, has led to a marked decrease of the eradication rates of traditional therapies. In previous works, we have validated the essential protein HsrA as an effective therapeutic target for H. pylori infection. HsrA is an OmpR/PhoB-type orphan response regulator, unique and highly conserved in members of phylum Campylobacterota, which appears involved in a variety of crucial physiological processes. In the present work, we carried out a transcriptomic analysis in order to discern the global effects of lethal concentrations of a bactericidal HsrA inhibitor on the H. pylori physiology. Treatment with the bactericidal HsrA inhibitor significantly changed the transcript levels of 367 open reading frames (ORF), of which 212 genes appeared upregulated and 155 genes resulted in downregulation, as compared with control samples. Thus, in vivo HsrA inhibition influenced, directly or indirectly, the expression of 23% of ORFs encoded by the H. pylori 26696 genome. Among the 268 differentially expressed genes (DEGs) with defined functions, two functional categories were highly enriched with downregulated genes involved in essential physiological processes: (1) ribosome biogenesis, and (2) electron transfer and oxidative phosphorylation.