Abstract 5558: MicroRNA Regulation of Endothelial Cell Growth

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Munekazu Yamakuchi ◽  
Marcella Ferlito ◽  
Charles J Lowenstein
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Growth ◽  
Genotoxic Stress ◽  
Luciferase Assay ◽  
Transcriptional Level ◽  
Sirt1 Expression ◽  
Over Expression ◽  
Endothelial Cell Growth ◽  
Foxo Transcription Factors

MicroRNAs (miRNAs) are short non-coding RNAs which inhibit gene expression at the post-transcriptional level. MiRNAs affect a wide variety of cellular functions such as proliferation, differentiation, and apoptosis, but the role of miRNA in endothelial cells is not well understood. The silent information regulator 1 (SIRT1) is an NAD-dependent deacetylase that regulates not only life-span but also cell growth arrest or apoptosis in response to oxidative and genotoxic stress. SIRT1 suppresses apoptosis thresholds by deacetylating molecular targets such as p53, FOXO transcription factors, and Ku70. We hypothesized that miRNA-34a regulates endothelial cell growth and senescence. We discovered that human endothelial cells (HUVEC and HAEC) express miRNA-34a by microarray analysis. When we over-expressed miR-34a in HUVEC, we found that SIRT1 protein was decreased. In contrast, transfection of HUVEC with antagomirs to miR-34a decreased endogenous miR-34a and increased SIRT1 protein. We identified a miR-34a binding site in the 3′ untranslated region (3′UTR) of SIRT1 and showed miR-34a directly inhibits SIRT1 translation using a luciferase assay. Next we examined the effect of miR-34a upon cell growth and senescence. Over-expression of miR-34a decreased SIRT1 protein, increased acetylated p53, and increased expression of p21, a transcriptional target of p53. When we co-transfected HUVEC with miR-34a precursor and SIRT1 expression vector to rescue SIRT1 expression, acetylated p53 and p21 expression were decreased. Finally over-expression of miR-34a induced cell cycle arrest and senescence in HUVEC using FACS and SA-gal assay. Our data suggest that miR-34a regulates cell growth and senescence through a SIRT1 - p53 pathway.

Abstract 3640: Mitochondrial Uncoupling Protein 2 Facilitates Endothelial Cell Growth and Angiogenesis via Reduction of Mitochondrial Superoxide

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Yukio Shimasaki ◽  
Kai Chen ◽  
John F Keaney
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Growth ◽  
Mitochondrial Function ◽  
Endothelial Cell Proliferation ◽  
Wild Type ◽  
Sprouting Angiogenesis ◽  
Mitochondrial Superoxide ◽  
Endothelial Cell Growth ◽  
Aortic Explants

Background: Growing evidence suggests that mitochondrial function contributes to cell phenotype. One important component of mitochondrial function is the membrane potential that is controlled, in part, by uncoupling proteins (UCPs). Based on our previous data, the UCP2 is predominantly expressed in cultured endothelial cells. Therefore, we sought to examine the role of UCP2 in endothelial cell growth and angiogenesis. Methods and Results: Murine lung endothelial cells (MLECs) were isolated from UCP2-null and wild-type mice. UCP2-null cells were found less proliferative than wild-type cells (P<0.02, UCP2-null cells vs. wild-type cells, n=4). This defect of UCP2-null cells was rescued by UCP2 adenovirus transfection (19% increase, p<0.02 vs. LacZ adenovirus treated cells, n=3), and also rescued by transfection with manganese superoxide dismutase (MnSOD) adenovirus (53% increase, P<0.002 vs. LacZ adenovirus treated cells, n=3). We found a reciprocal relation such as no UCP2 expression and higher mitochondrial superoxide level in the MLECs (P<0.005, UCP2-null cells vs. wild-type cells, n=3), suggesting that mitochondrial superoxide may regulate endothelial cell growth. Then, we prepared murine aortic rings from UCP2-null and wild-type mice and embedded in rat tail collagen gel. The sprouting angiogenesis of UCP2-null explants was significantly less than wild-type explants (P<0.02, UCP2-null explants vs. wild-type explants, n=3– 4). Furthermore, MLECs from MnSOD-heterozygous mice showed less proliferation with lower expression of UCP2 protein and higher mitochondrial superoxide level compared to the MLECs from wild-type littermates (P<0.02, MnSOD-heterozygous cells vs. wild-type cells, n=4 – 8). We also observed less sprouting angiogenesis in MnSOD-heterozygous aortic explants than wild-type aortic explants (P<0.05, MnSOD-heterozygous explants vs. wild-type explants, n=3– 6). Conclusions: These data indicate that mitochondrial superoxide controls endothelial cell proliferation and angiogenesis, suggesting that mitochondrial metabolism modulates the endothelial cell growth and angiogenesis.

scholarly journals LncRNA GATA6-AS inhibits cancer cell proliferation and promotes cancer cell apoptosis in cervical cancer by down-regulating miR-205

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaoying Zhao ◽  
Huzhong Zheng ◽  
Jun Chen
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Endothelial Cell ◽  
Cell Growth ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Human Cancer ◽  
Over Expression ◽  
Endothelial Cell Growth ◽  
Healthy Females

Abstract Background Dysregulated endothelial cell growth is involved in many types of human cancer, including cervical cancer. LncRNA GATA6-AS was reported to regulate endothelial cell growth, suggesting it might involve in cervical cancer. Our study was carried out to explore the involvement of GATA6-AS in cervical squamous cell carcinoma (CSCC), a subtype of cervical cancer. Methods To explore the expression of GATA6-AS, RT-qPCR was performed to detect GATA6-AS in plasma of 65 CSCC patients and 58 healthy females. To detect the expression of GATA6-AS, total RNAs were extracted. Results We found that plasma GATA6-AS expression was down-regulated in CSCC patients than that in healthy females, and HPV infection did not significantly affect the plasma expression of GATA6-AS. Moreover, we found that plasma GATA6-AS showed diagnostic values for CSCC by performing ROC curve analysis. The expression of miR-205 in plasma was also found to be up-regulated in CSCC patients than that in healthy females and inversely correlated with the expression of GATA6-AS in CSCC patients. Furthermore, over-expression of miR-205 did not significantly affect the expression of GATA6-AS in CSCC cells, while over-expression of GATA6-AS down-regulated miR-205 expression. In addition, GATA6-AS over-expression inhibited CSCC cell proliferation and promoted CSCC cell apoptosis, while miR-205 over-expression played opposite roles and attenuated the effects of GATA6-AS over-expression on CSCC cells. Conclusion Taken together, these results suggest that GATA6-AS may inhibit cell proliferation and promote cell apoptosis in CSCC by down-regulating miR-205.

Activation of a procollagenase by low-molecular-weight angiogenesis factor

1983 ◽  
Vol 3 (2) ◽  
pp. 171-177 ◽  
Author(s):  
Jacqueline B. Weiss ◽  
C. R. Hill ◽  
R. J. Davis ◽  
B. McLaughlin ◽  
K. A. Sedowofia ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Growth ◽  
Low Molecular Weight ◽  
Type I ◽  
Angiogenesis Factor ◽  
The Matrix ◽  
Endothelial Cell Growth

Avascular tumours have the ability to establish a blood supply for themselves by secreting a humoral factor which stimulates their host's endothelial cells to proliferate and to migrate towards the tumour source. The mechanism of action of such a humoral anglo-genesis factor is more than that of an endothelial-cell growth factor since it requires an oriented migration of cells towards the tumour. We report here the activation of pure skin-fibroblast procollagenase by a low-molecular-weight angiogenesis factor capable of stimulating endothelial-cell growth in vitro. The activation was observed when either Type I or III collagen was used as substrate. It is suggested that at least one function of angiogenesis factor is to promote limited degradation of the connective tissue through which it passes causing channeling in the matrix along which stimulated endothelial cells may

Adenosine stimulates proliferation of human endothelial cells in culture

1993 ◽  
Vol 265 (1) ◽  
pp. H131-H138 ◽  
Author(s):  
M. F. Ethier ◽  
V. Chander ◽  
J. G. Dobson
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Growth ◽  
Cell Cultures ◽  
Umbilical Vein ◽  
Fibroblast Cell ◽  
Human Endothelial Cells ◽  
Cell Counts ◽  
Endothelial Cell Cultures ◽  
Endothelial Cell Growth

The effect of adenosine on proliferation of human endothelial cells was investigated by adding adenosine to the medium of cultures derived from human umbilical veins. Cell counts on cultures grown in 10 microM adenosine for 4–7 days were 41–53% greater than counts from control cultures. In contrast, 10 microM adenosine had no effect on growth of a human fibroblast cell strain (IMR-90). Neither inosine nor 2',5'-dideoxyadenosine influenced endothelial cell growth at concentrations of 0.1 or 10 microM. Addition of adenosine deaminase abolished the proliferative effect of added adenosine and inhibited proliferation by 16% in control cultures, suggesting that endogenous adenosine may enhance proliferation in culture. The adenosine receptor antagonist, 8-phenyltheophylline, at 0.1 and 1.0 microM blocked the enhanced proliferation caused by 10 microM adenosine. Addition of 10 microM adenosine enhanced DNA synthesis in endothelial cell cultures as indicated by an increased incorporation of [3H]thymidine into acid-insoluble cell material. The results indicate that addition of physiological concentrations of adenosine to human umbilical vein endothelial cell cultures stimulates proliferation, possibly via a surface receptor, and suggest that adenosine may be a factor for human endothelial cell growth and possibly angiogenesis.

Attributes of Antiangiogenic Factor Plasminogen Kringle 5 in Glomerulonephritis

2010 ◽  
Vol 134 (12) ◽  
pp. 1804-1812
Author(s):  
Jin-Shuen Chen ◽  
Jyh-Chang Hwang ◽  
Li-Chien Chang ◽  
Chia-Chao Wu ◽  
Yuh-Feng Lin
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Growth ◽  
Focal Segmental Glomerulosclerosis ◽  
Animal Study ◽  
Human Subjects ◽  
Kringle Domain ◽  
Segmental Glomerulosclerosis ◽  
Glomerular Endothelial Cells ◽  
Endothelial Cell Growth

Abstract Context—Plasminogen kringle domain (K) 5 is known to inhibit endothelial cell growth, but limited data are available investigating the relationship between K5 and glomerulonephritis (GN). Objective—To understand the relationships among K5, GN, and glomerular endothelial cells in GN mice models and human subjects. Design—Two mice models of GN and 2 categories of human GN biopsy samples were collected to gain insight into the disease mechanism from the laboratory to bedside. In the mechanistic animal study, membranous nephropathy (MN) and focal segmental glomerulosclerosis mice models were used. Kringle domain 5 in the diseased kidney was located by immunofluorescence and quantified by Western blotting. In the kinetic animal study, different MN time points were stained with K5, immunoglobulin G, and C3 by immunofluorescence. CD31 and proliferating cell nuclear antigen were evaluated by immunohistochemical double staining for alterations in the glomerular endothelial cells. Biopsy samples from patients diagnosed with antibody (Ab)-mediated and non-Ab–mediated GN were collected for K5 analysis. Results—The expression level of K5 was found to be significant in MN, but not in focal segmental glomerulosclerosis, and was markedly elevated in the diseased glomeruli along the capillary walls. Kringle domain 5 levels increased steadily with the evolution of MN, appearing after the deposition of Abs. In altered glomerular endothelial cells, CD31 decreased with the evolution of MN. In human subjects, K5 occurred only in patients with Ab GN. Conclusions—Kringle domain 5 might be involved in the progression of Ab-mediated GN and associated with the alteration of MN glomerular endothelial cell growth.

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