scholarly journals Identification of a novel regulatory pathway for PPARα by RNA-seq characterization of the endothelial cell lipid peroxidative injury transcriptome

Open Biology ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 190141
Author(s):  
Fangfang Dou ◽  
Beiling Wu ◽  
Lin Sun ◽  
Jiulin Chen ◽  
Te Liu ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Protein Interactions ◽  
Cell Injury ◽  
Enrichment Analysis ◽  
Rna Seq ◽  
Ppi Network ◽  
Endothelial Cell Injury ◽  
Expression Levels ◽  
String Database ◽  
Cell Lipid

Endothelial dysfunction caused by endothelial cell injuries is the initiating factor for atherosclerosis (AS), and lipid peroxidative injury is one of a dominant factor for AS pathogenesis. Using RNA-seq, we compared changes in transcriptome expression before and after endothelial cell injury, and found 311 differentially expressed genes (DEGs), of which 258 genes were upregulated and 53 genes were downregulated. The protein–protein interactions (PPIs) between the genes were analysed using the STRING database, and a PPI network of DEGs was constructed. The relationship distributions among these PPIs were analysed by performing network node statistics. We found that in the top 20 DEGs with high connected protein nodes in the PPI network, 16 were upregulated and 4 were downregulated. Gene ontology (GO) functional enrichment analysis and KEGG pathway enrichment analysis on the DEGs were also performed. By comparing the upregulated expressed genes with high connected protein nodes in the PPI network to those related to endothelial cell lipid damage and repair in the GO analysis, we identified seven genes (NOX4, PPARA, CCL2, PDGFB, IL8, VWF, CD36) and verified their expression levels by real-time polymerase chain reaction. The protein interactions between the seven genes were then analysed using the STRING database. The results predicted that CCL2 interacts with NOX4, PPARα, PDGFβ and VWF individually. Thus, we examined the protein expression levels of CCL2, NOX4, PPARα, PDGFβ and VWF, and found that the expression levels of all proteins were significantly upregulated after the lipid peroxidative injury, with CCL2 and PPARα exhibiting the highest expression levels. Therefore, we investigated the interregulatory relationship between CCL2 and PPARα and their roles in the repair of endothelial cell injury. With the help of gene overexpression and knockdown techniques, we discovered that PPARα promotes the repair of endothelial cell injury by upregulating CCL2 expression in human umbilical vein endothelial cells but that CCL2 cannot regulate PPARα expression. Therefore, we believe that PPARα participates in the repair of endothelial cell lipid peroxidative injury through regulating the expression of CCL2.

scholarly journals Genistein Inhibited Estradiol-Induced Vascular Endothelial Cell Injury by Downregulating the FAK/Focal Adhesion Pathway

2018 ◽  
Vol 49 (6) ◽  
pp. 2277-2292 ◽  
Author(s):  
Bing Liu ◽  
Lili Xu ◽  
Xinming Yu ◽  
Xuefei Jiao ◽  
Junwei Yan ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Focal Adhesion ◽  
Cell Invasion ◽  
Cell Injury ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Endothelial Cell Injury ◽  
Expression Levels ◽  
Invasion And Migration ◽  
And Migration

Background/Aims: In this study, we aimed to investigate the effects of genistein on the focal adhesion signaling pathway through its regulation of FAK. Genistein ultimately restored and alleviated estradiol-induced vascular endothelial injury. Methods: Microarray analysis was used to select differentially expressed genes. MTT assay was performed to detect the cell activity, and ROS test and NO test were performed to detect the degree of damage to HUVECs (human umbilical vein endothelial cells). The relative mRNA expression levels and protein expression levels of FAK were tested by western blot and qRT-PCR. GO functional analysis and KEGG pathway analysis were applied to predict the possible relationship between functions and related pathways, and transwell assay was used to detect cell invasion and migration. Results: FAK was highly expressed in the HUVECs treated with estradiol (HU-ESTs). Cell viability and NO level decreased, whereas ROS level increased in the HU-ESTs. Effective knockdown of FAK in HU-ESTs elevated cell viability and NO levels while suppressing ROS levels. In addition, inhibition of FAK greatly decreased cell invasion and migration, while the overexpression of FAK enhanced cell invasion and migration. KEGG further indicated focal adhesion pathways were activated. Genistein elevated HU-EST viability, and NO and ROS level increased in a concentration dependent manner. Transwell and western blot assays revealed that genistein could reduce the FAK expression levels and alleviate the damage to the HU-ESTs. Conclusion: FAK overexpression promoted invasion and migration of the HU-ESTs. However, genistein greatly suppressed FAK and estradiol-induced vascular endothelial cell injury.

507-P: Changes of miR-223-3p May Play an Important Role in Renal Endothelial Cell Injury of Diabetes Kidney Disease (DKD)

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 507-P
Author(s):  
RONG LI ◽  
LIN JIE ◽  
JINGMEI LUO ◽  
ZHONGCE YANG ◽  
LIHUA ZHANG
Keyword(s):  
Endothelial Cell ◽  
Kidney Disease ◽  
Cell Injury ◽  
Endothelial Cell Injury

scholarly journals The severity of glomerular endothelial cell injury is associated with infiltrating macrophage heterogeneity in endocapillary proliferative glomerulonephritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Momoko Arai ◽  
Akiko Mii ◽  
Tetsuya Kashiwagi ◽  
Akira Shimizu ◽  
Yukinao Sakai
Keyword(s):  
Endothelial Cell ◽  
Cell Injury ◽  
Cell Damage ◽  
Computer Assisted ◽  
Endothelial Cell Injury ◽  
Glomerular Capillary ◽  
Luminal Area ◽  
Endocapillary Proliferative Glomerulonephritis ◽  
Cell Phenotypes ◽  
Schonlein Purpura

AbstractEndocapillary proliferation occurs in various types of glomerulonephritis (GN), with varying prognoses. We examined 42 renal biopsy samples representing endocapillary proliferative lesions from post-streptococcal acute GN (PSAGN), Henoch–Schönlein purpura nephritis (HSPN), and lupus nephritis (LN). In PSAGN, the glomerular capillary network was maintained, although severe lesions displayed dots or short, curved lines, indicating CD34-positive capillaries and suggesting capillary obstruction. Conversely, patients with LN and HSPN displayed obstruction of CD34-positive capillaries with dissociation from the glomerular basement membrane even in mild lesions. According to computer-assisted morphologic analysis, the cell density did not differ between the diseases. However, in PSAGN, the number of capillary loops was significantly increased, with a larger glomerular capillary luminal area than in the other groups. In addition, the number and frequency of CD163-positive cells (M2 macrophages) tended to be higher in PSAGN, while there were no significant differences in the number of CD68-positive (total) macrophages. These results indicate that in PSAGN, endothelial cell damage is less severe, and angiogenesis may be promoted. The severity of endothelial cell injury in each disease may be associated with differences in infiltrating inflammatory cell phenotypes.

Prognostic Significance of Plasma Hepatocyte Growth Factor in Sepsis

2021 ◽  
pp. 088506662199342
Author(s):  
Fei Peng ◽  
Chenglong Liang ◽  
Wei Chang ◽  
Qin Sun ◽  
Jianfeng Xie ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cell Injury ◽  
Prognostic Significance ◽  
Trial Registration ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pulmonary Vascular Permeability ◽  
Endothelial Cell Injury ◽  
Hepatocyte Growth

Background: To assess any correlation of plasma hepatocyte growth factor (HGF) levels with relevant endothelial cell injury parameters and determine the prognostic value in septic patients. Methods: A prospective, observational study was conducted in patients with sepsis admitted to the Department of Critical Care Medicine at the Zhongda Hospital from November 2017 to March 2018. Plasma HGF levels were measured by enzyme-linked immunosorbent assay in the first 24 h after admission (day 1) and on day 3. The primary endpoint was defined as all-cause 28-day mortality. Furthermore, we analyzed the correlation of HGF with relevant endothelial cell injury markers. Results: Eighty-six patients admitted with sepsis were included. HGF levels of nonsurvivors were elevated compared to those of survivors on day 1 (1940.62 ± 74.66 pg/mL vs. 1635.61 ± 47.49 pg/mL; P = 0.002) and day 3 (1824.82 ± 137.52 pg/mL vs. 1309.77 ± 83.49 pg/mL; P = 0.001) and showed a strong correlation with von Willebrand factor (r = 0.45, P < 0.0001), lactate (r = 0.35, P = 0.0011), pulmonary vascular permeability index (r = 0.38, P = 0.0241), first 24 h fluid administration (r = 0.38, P < 0.0001), and sequential organ failure assessment score (r = 0.40, P = 0.0001). Plasma HGF levels were able to prognostically discriminate between survivors and nonsurvivors on day 1 (AUC: 0.72, 95%CI: 0.60-0.84) and day 3 (AUC: 0.77, 95%CI: 0.63-0.91). Conclusions: HGF levels are associated with sepsis and correlated with established markers of endothelial cell injury. Elevated HGF levels in sepsis patients are an efficient indicator of poor prognosis. Trial registration: The study was registered in Clinical Trial (Registration Number: NCT02883231).

scholarly journals Kaempferol alleviates human endothelial cell injury through circNOL12/miR-6873-3p/FRS2 axis

2021 ◽  
Vol 137 ◽  
pp. 111419
Author(s):  
Shuangzhan Li ◽  
Meihua Hao ◽  
Taisheng Wu ◽  
Zixuan Wang ◽  
Xicheng Wang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Injury ◽  
Human Endothelial Cell ◽  
Endothelial Cell Injury

Laser-induced shock wave endothelial cell injury

2000 ◽  
Vol 26 (4) ◽  
pp. 364-375 ◽  
Author(s):  
Anders Sond�n, ◽  
Bengt Svensson ◽  
Nils Roman ◽  
Henric �stmark ◽  
Bo Brismar ◽  
...  
Keyword(s):  
Shock Wave ◽  
Endothelial Cell ◽  
Cell Injury ◽  
Endothelial Cell Injury
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