scholarly journals CRP Stimulates GDF15 Expression in Endothelial Cells through p53

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Yoonseo Kim ◽  
Nicole Noren Hooten ◽  
Michele K. Evans
Keyword(s):  
Endothelial Cells ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Aortic Endothelial Cells ◽  
Reactive Protein ◽  
Direct Target Gene ◽  
Reporter Assays ◽  
Direct Target ◽  
Human Aortic Endothelial Cells

Growth differentiation factor 15 (GDF15) is a multifunctional, secreted protein that is a direct target gene of p53. GDF15 is a prospective biomarker of cardiovascular disease (CVD). C-reactive protein (CRP), like GDF15, is implicated in inflammation and an independent biomarker of CVD. However, the molecular interactions between GDF15 and CRP remain unexplored. In women, we found a significant relationship between hsCRP and GDF15 serum and mRNA levels. In vitro treatment of cultured human aortic endothelial cells (HAECs) with purified CRP or transfection of a CRP plasmid into HAECs induced GDF15 expression. Dual-luciferase reporter assays confirmed that CRP significantly increased the levels of GDF15 promoter luciferase activity, indicating that CRP induces GDF15 transcription. Chromatin immunoprecipitation (ChIP) assays confirmed that p53 was recruited to both p53 binding sites 1 and 2 in the GDF15 promoter in response to CRP. We have uncovered a linkage between CRP and GDF15, a new clue that could be important in the pathogenesis of endothelial inflammation.

MicroRNA-183 as a Novel Regulator Protects Against Cardiomyocytes Hypertrophy via Targeting TIAM1

2020 ◽  
Author(s):  
Fu-han Gong ◽  
Xi-Lu Chen ◽  
Quan Zhang ◽  
Xiao-qiang Xiao ◽  
Yong-sheng Yang ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Bioinformatics Analysis ◽  
Negative Control ◽  
Neonatal Rat ◽  
Luciferase Reporter ◽  
Ang Ii ◽  
Direct Target Gene ◽  
Phenotype Analysis ◽  
Reporter Assays

Abstract BACKGROUND MicroRNAs serve as important regulators of the pathogenesis of cardiac hypertrophy. Among them, miR-183 is well documented as a novel tumor suppressor in previous studies, whereas it exhibits a downregulated expression in cardiac hypertrophy recently. The present study was aimed to examine the effect of miR-183 on cardiomyocytes hypertrophy. METHODS Angiotensin II (Ang II) was used for establishment of cardiac hypertrophy model in vitro. Neonatal rat ventricular cardiomyocytes transfected with miR-183 mimic or negative control were further utilized for the phenotype analysis. Moreover, the bioinformatics analysis and luciferase reporter assays were used for exploring the potential target of miR-183 in cardiomyocytes. RESULTS We observed a significant decreased expression of miR-183 in hypertrophic cardiomyocytes. Overexpression of miR-183 significantly attenuated the cardiomyocytes size morphologically and prohypertrophic genes expression. Moreover, we demonstrated that TIAM1 was a direct target gene of miR-183 verified by bioinformatics analysis and luciferase reporter assays, which showed a decreased mRNA and protein expression in the cardiomyocytes transfected with miR-183 upon Ang II stimulation. Additionally, the downregulated TIAM1 expression was required for the attenuated effect of miR-183 on cardiomyocytes hypertrophy. CONCLUSIONS Taken together, these evidences indicated that miR-183 acted as a cardioprotective regulator for the development of cardiomyocytes hypertrophy via directly regulation of TIAM1.

Activation of human aortic endothelial cells by LDL from Type 1 diabetic patients: an in vitro study

2002 ◽  
Vol 165 (1) ◽  
pp. 69-77 ◽  
Author(s):  
Rosa A Rabini ◽  
Arianna Vignini ◽  
Eleonora Salvolini ◽  
Roberto Staffolani ◽  
Daniela Martarelli ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
In Vitro Study ◽  
Vitro Study ◽  
Diabetic Patients ◽  
Aortic Endothelial Cells ◽  
Type 1 Diabetic Patients ◽  
Human Aortic Endothelial Cells ◽  
Aortic Endothelial

scholarly journals Demonstration That C-Reactive Protein Decreases eNOS Expression and Bioactivity in Human Aortic Endothelial Cells

Circulation ◽  
2002 ◽  
Vol 106 (12) ◽  
pp. 1439-1441 ◽  
Author(s):  
Senthil Kumar Venugopal ◽  
Sridevi Devaraj ◽  
Ivan Yuhanna ◽  
Philip Shaul ◽  
Ishwarlal Jialal
Keyword(s):  
Endothelial Cells ◽  
C Reactive Protein ◽  
Enos Expression ◽  
Aortic Endothelial Cells ◽  
Reactive Protein ◽  
Human Aortic Endothelial Cells ◽  
Aortic Endothelial

scholarly journals miR-20a regulates sensitivity of colorectal cancer cells to NK cells by targeting MICA

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Siwen Tang ◽  
Hongyu Fu ◽  
Qihua Xu ◽  
Ying Zhou
Keyword(s):  
Colorectal Cancer ◽  
Nk Cells ◽  
Luciferase Reporter ◽  
Normal Tissues ◽  
Histocompatibility Complex ◽  
Colorectal Cancer Cells ◽  
Reporter Assays ◽  
Direct Target ◽  
Causes Of Deaths

Abstract Colorectal cancer (CRC) is one of the leading cancer-related causes of deaths in the world. Recently, microRNAs have been reported to regulate the tumor growth, invasion and the immunosuppression. In the present study, we found that miR-20a was increased in human CRC specimens compared with the healthy normal tissues. However, miR-20a overexpression and knockdown did not impair the CRC cell growth in vitro. Our results indicated that CD107a+ NK cells are increased in CRC group. Furthermore, cytotoxicity assays demonstrated that miR-20a knockdown promoted the CRC cells sensitive to NK cells, whereas miR-20a overexpression showed the opposite results. Our results suggest that the regulation of NK cells by miR-20a depends on NKG2D. Luciferase reporter assays revealed that the NKG2D ligand Major Histocompatibility Complex (MHC) class I-related chain genes A (MICA) is the direct target of miR-20a. Flow cytometry showed the MICA protein level is significantly reduced in miR-20a-overexpressing CRC cells and increased in miR-20a knockdown CRC cells. Taken together, our results suggest that miR-20a regulates sensitivity of CRC cells to NK cells by targeting MICA.

Gene expression profiling of human aortic endothelial cells exposed to disturbed flow and steady laminar flow

2002 ◽  
Vol 9 (1) ◽  
pp. 27-41 ◽  
Author(s):  
Alan R. Brooks ◽  
Peter I. Lelkes ◽  
Gabor M. Rubanyi
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Laminar Flow ◽  
Mrna Levels ◽  
Monocyte Adhesion ◽  
Disturbed Flow ◽  
Aortic Endothelial Cells ◽  
Human Aortic Endothelial Cells ◽  
Steady Laminar

Subtraction cloning and cDNA arrays were used to compare steady-state mRNA levels in cultured human aortic endothelial cells (HAEC) exposed for up to 24 h to either high-shear (13 dyn/cm2) steady laminar flow (LF), an established representation of “atheroprotective” flow conditions, or low-shear (<1 dyn/cm2), pulsatile, nonsteady, non-unidirectional flow (disturbed flow, DF) that simulates conditions in the atherosclerosis-prone areas of the arterial circulation. More than 100 genes not previously known to be flow regulated were identified. Analysis of selected genes by quantitative RT-PCR confirmed the results obtained from the microarrays. These data demonstrate that DF is not simply the absence of LF but in fact represents a distinct biomechanical stimulus that has a profound impact upon the gene expression profile of HAEC in culture. In line with previous studies, many of the changes in mRNA levels induced by LF are atheroprotective. In contrast, DF upregulated the mRNA levels of a plethora of proatherosclerotic genes including proinflammatory, proapoptotic, and procoagulant molecules. For some of the genes whose expression was altered by DF and LF, corresponding changes in EC function (proliferation and monocyte adhesion) could be demonstrated. Specifically, the sustained upregulation of VCAM-1 and increased monocyte adhesion to EC exposed to DF was similar to that found in EC in vivo at atherosclerosis-prone regions, confirming the relevance of our model system for in vivo conditions. Distinct differences in the cellular response induced by TNFα and DF suggest that the effects of DF are not mediated entirely by the same signaling pathways that activate NF-κB. These studies demonstrate extensive and pathophysiologically relevant changes in sustained gene expression patterns in aortic EC exposed to DF compared with LF which are predicted to induce a proatherogenic EC phenotype.

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