Dataset Information

Long Non-coding RNA MEG3 Attenuates the Angiotensin II-Induced Injury of Human Umbilical Vein Endothelial Cells by Interacting With p53.

ABSTRACT: Angiotensin II (Ang II)-induced damage to endothelial cells (ECs) plays a crucial role in the pathogenesis of cardiovascular disease. This study aimed to investigate the role of maternally expressed gene 3 (Meg3) in endothelial cell injury. A lncRNA human gene expression microarray analysis was used to identify differentially expressed lncRNAs in human umbilical vein endothelial cell (HUVECs). Cell viability, apoptosis, and migration were then assessed Ang II-treated HUVECs. qRT-PCR and western blotting were performed to detect the expression level of p53 after Meg3 knockdown and overexpression. We observed that Ang II treatment decreased the Meg3 level in HUVECs. Next, both knockdown of Meg3 and Ang II decreased cell viability, increased apoptotic cell rate and impair migration function in HUVECs. Furthermore, overexpression of Meg3 inhibited cell apoptosis, and increased cell migration by enhancing p53 transcription on its target genes, including CRP, ICAM-1, VEGF, and HIF-1?. Our findings indicate that Meg3 might be associated with cardiovascular disease development.

SUBMITTER: Song J

PROVIDER: S-EPMC6389612 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Long Non-coding RNA MEG3 Attenuates the Angiotensin II-Induced Injury of Human Umbilical Vein Endothelial Cells by Interacting With p53.

Song Jingwen J Huang Songqun S Wang Kaizhong K Li Wei W Pao Lizhi L Chen Feng F Zhao Xianxian X

Frontiers in genetics 20190219

Angiotensin II (Ang II)-induced damage to endothelial cells (ECs) plays a crucial role in the pathogenesis of cardiovascular disease. This study aimed to investigate the role of maternally expressed gene 3 (Meg3) in endothelial cell injury. A lncRNA human gene expression microarray analysis was used to identify differentially expressed lncRNAs in human umbilical vein endothelial cell (HUVECs). Cell viability, apoptosis, and migration were then assessed Ang II-treated HUVECs. qRT-PCR and western ...[more]

PMID: 30838022

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Project description:Autophagy is a conserved catabolic process by which cytoplasmic components are delivered into lysosomes for degradation. Pigment epithelium‑derived factor (PEDF) has been reported to be associated with autophagy and can induce p53 expression; however, the mechanism relating PEDF with autophagy in endothelial cells remains poorly understood. The present study aimed to investigate the association between the PEDF‑p53‑sestrin pathway and autophagy in human umbilical vein endothelial cells (HUVECs). PEDF‑induced autophagy was examined by fluorescence microscopy and western blot analysis. p53 small interfering (si)RNA and sestrin2 siRNA were constructed and transfected into HUVECs prior to PEDF treatment. The protein expression levels of microtubule‑associated protein light chain 3 (LC3) I, LC3 II and p62 were evaluated by western blot analysis, and the mRNA expression levels of p53 and sestrin2 were determined using reverse transcription‑quantitative polymerase chain reaction analysis. The regulation of mechanistic target of rapamycin (mTOR) was reflected by p70S6 kinase (p70S6K) and eukaryotic translation initiation factor 4E‑binding protein 1 (4E‑BP1) protein expression levels, as determined by western blot analysis. PEDF could induce HUVEC autophagy by sequentially inducing p53 and sestrin2 expression, as observed by fluorescence microscopy and western blot analysis. Conversely, the induction of sestrin2 by PEDF was eliminated by p53 siRNA. In addition, p53 siRNA and sestrin2 siRNA could attenuate PEDF‑induced HUVEC autophagy. Inhibition of mTOR may be the mechanism responsible for PEDF‑induced autophagy; as p70S6K and 4E‑BP1 phosphorylation levels were significantly upregulated in p53 siRNA‑treated and sestrin2 siRNA‑treated groups. The findings of the present study indicated that PEDF may trigger autophagy in HUVECs by inducing p53 and sestrin2 expression, and inhibiting mTOR expression; these findings may contribute to the improved understanding of diseases, including cancer and atherosclerosis.

Project description:Background: Qingda granules (QDG) exhibit antihypertension and multiple-target-organ protection. However, the therapeutic potential of QDG on hypertensive renal injury remains unknown. Therefore, the main objective of the current study is to explore the effects and underlying mechanisms of QDG treatment on renal injury in angiotensin (Ang) II-infused mice. Methods and results: Mice were infused with Ang II (500 ng/kg/min) or saline for 4 weeks with subcutaneously implanted osmotic pumps. After infusion, mice in the Ang II + QDG group were intragastrically administrated with QDG daily (1.145 g/kg/day), whereas the control group and Ang II group were intragastrically administrated with the same amount of double-distilled water. Blood pressure of the mice monitored using the CODA™ noninvasive blood pressure system revealed that QDG treatment significantly attenuated elevated blood pressure. Moreover, hematoxylin-eosin staining indicated that QDG treatment ameliorated Ang II-induced renal morphological changes, including glomerular sclerosis and atrophy, epithelial cell atrophy, and tubular dilatation. RNA-sequencing (RNA-seq) identified 662 differentially expressed transcripts (DETs) in renal tissues of Ang II-infused mice, which were reversed after QDG treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis based on DETs in both comparisons of Ang II vs. Control and Ang II + QDG vs. Ang II identified multiple enriched pathways, including apoptosis and p53 pathways. Consistently, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining and Annexin V staining revealed that QDG treatment significantly attenuated Ang II-induced cell apoptosis in renal tissues and cultured renal tubular epithelial cell lines (NRK-52E). Furthermore, western blot analysis indicated that Ang II infusion significantly upregulated the protein expression of p53, BCL2-associated X (BAX), cle-caspase-9, and cle-caspase-3, while downregulating the protein expression of BCL-2 in renal tissues, which were attenuated after QDG treatment. Conclusion: Collectively, QDG treatment significantly attenuated hypertensive renal injury, partially by attenuating renal apoptosis and suppressing p53 pathways, which might be the underlying mechanisms.

Project description:Background/aimsOxidative stress-induced damage in endothelial cells is a crucial initiator of atherosclerosis (AS), which is highly related to excessive reactive oxygen species (ROS) and mitochondrial dynamics. Resveratrol (RSV) exerts beneficial effects against endothelial oxidative injury, while the underlying mechanisms have not been fully elucidated. Thus, we aimed to explore the role of mitochondria dynamics during the anti-oxidative activities of RSV in palmitic acid (PA)-stimulated human umbilical vein endothelial cells (HUVECs) and to verify whether tyrosyl transfer- RNA synthetase (TyrRS) and poly (ADP-ribose) polymerase 1 (PARP1) are targeted during this process.MethodsHUVECs were exposed to 200 μM of PA for 16 h before treated with 10 μM of RSV for 8 h. Cell viability was detected using Cell counting kit-8 (CCK-8) assay. The intracellular ROS level and mitochondria membrane potential (MMP) were measured using microplate reader and flow cytometry. The malondialdehyde and superoxide dismutase were measured using the microplate reader. The mitochondrial morphology and fusion process was observed under transmission electron microscopy and confocal microscopy. TyrRS and PARP1 were knocked down with the specific small interference RNAs (siRNA), and the protein expressions of TyrRS, PARP1, and mitochondrial fusion proteins (MFN1, MFN2, and OPA1) were measured by western blot.ResultsRSV treatment suppressed the PA-induced injuries in HUVECs, including the damage to cell viability, oxidative stress, and loss of MMP. Additionally, RSV improved the protein levels of MFN1, MFN2, and OPA1 as well as inhibited the PA-induced fragmentation of mitochondria. However, the effects of RSV on oxidative stress and mitochondrial fusion were abolished by the pretreatment of siRNAs of TyrRS and PARP1, indicating that these effects of RSV were dependent on the TyrRS-PARP1 pathway.ConclusionsRSV attenuated endothelial oxidative injury by regulating mitochondrial fusion via TyrRS-PARP1 signaling pathway.

Dataset Information

Long Non-coding RNA MEG3 Attenuates the Angiotensin II-Induced Injury of Human Umbilical Vein Endothelial Cells by Interacting With p53.

Publications

Long Non-coding RNA MEG3 Attenuates the Angiotensin II-Induced Injury of Human Umbilical Vein Endothelial Cells by Interacting With p53.

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