Epigenetic control of hypoxia inducible factor-1α-dependent expression of placental growth factor in hypoxic conditions

Tudisco, Laura; Ragione, Floriana Della; Tarallo, Valeria; Apicella, Ivana; D’Esposito, Maurizio; Matarazzo, Maria R.; Falco, Sandro De

doi:10.4161/epi.27835

Cited by 35 publications

(27 citation statements)

References 59 publications

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“…Both systems, a transcription factor and an epigenetic regulator, are being regulated by hypoxia [82]. Further, HIF-1α has been suggested as an epigenetic modulator determining chromatin remodeling of hypoxia-responsive elements (HREs) sites [83]. Interestingly, in this report, a marked hyperacetylation of histones H3 and H4 was observed in the placental growth factor (Plgf) intron in hypoxic conditions.…”

Section: Epigenetics and Endothelial Dysfunctionsupporting

confidence: 47%

Epigenetic Programming of Cardiovascular Disease by Perinatal Hypoxia and Fetal Growth Restriction

Casanello¹,

Herrera²,

Krause³

2017

Hypoxia and Human Diseases

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Most of the worldwide deaths in patients with non-communicable diseases are due to cardiovascular and metabolic diseases, which are determined by a mix of environmental, genetic and epigenetic factors, and by their interactions. The aetiology of most cardiovascular diseases has been partially linked with in utero adverse conditions that may increase the risk of developing diseases later in life, known as Developmental Origins of Health and Disease (DOHaD). Perinatal hypoxia can program the fetal and postnatal developmental patterns, resulting in permanent modifications of cells, organs and systems function. In spite of the vast evidence obtained from human and animal studies linking development under adverse intrauterine conditions with increased cardiovascular risk, still few is known about the specific effects of intrauterine oxygen deficiency and the related pathogenic mechanisms. Currently, the most accepted processes that program cellular function are epigenetic mechanisms which determine gene expression in a cell-specific fashion. In this chapter we will review the current literature regarding the perinatal exposure to chronic hypoxia and Fetal Growth Restriction (FGR) in humans and animals and how this impinges the cardiovascular physiology through epigenetic, biochemical, morphologic and pathophysiologic modifications that translate into diseases blasting at postnatal life.

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Section: Epigenetics and Endothelial Dysfunctionsupporting

confidence: 47%

Epigenetic Programming of Cardiovascular Disease by Perinatal Hypoxia and Fetal Growth Restriction

Casanello¹,

Herrera²,

Krause³

2017

Hypoxia and Human Diseases

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“…Thus, Ang-(1-7) might reduce VEGF-A expression by inhibition of MAPK signaling. HIF-1α increases VEGF-A expression and also upregulates other proangiogenic factors, such as placental growth factor (PIGF) (46). Ang-(1-7) has been confirmed to reduce the expression of the HIF-1α gene (47), which suggests that HIF-1α may be a key mediator of Ang-(1-7) in regulating angiogenesis.…”

Section: Discussionmentioning

confidence: 89%

Angiotensin-(1–1) Suppresses Hepatocellular Carcinoma Growth and Angiogenesis via Complex Interactions of Angiotensin II Type 1 Receptor, Angiotensin II Type 2 Receptor and Mas Receptor

Liu

Wang

et al. 2015

Mol Med

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We recently confirmed that angiotensin II (Ang II) type 1 receptor (AT 1 R) was overexpressed in hepatocellular carcinoma tissue using a murine hepatoma model. Angiotensin(Ang)-(1-7) has been found beneficial in ameliorating lung cancer and prostate cancer. Which receptor of Ang-(1-7) is activated to mediate its effects is much speculated. This study was designed to investigate the effects of Ang-(1-7) on hepatocellular carcinoma, as well as the probable mechanisms. H22 hepatoma-bearing mice were randomly divided into five groups for treatment: mock group, low-dose Ang-(1-7), high-dose Ang-(1-7), high-dose Ang-(1-7) + A779 and high-dose Ang-(1-7) + PD123319. Ang-(1-7) treatment inhibited tumor growth time-and dose-dependently by arresting tumor proliferation and promoting tumor apoptosis as well as inhibiting tumor angiogenesis. The effects of Ang-(1-7) on tumor proliferation and apoptosis were reversed by coadministration with A779 or PD123319, whereas the effects on tumor angiogenesis were completely reversed by A779 but not by PD123319. Moreover, Ang-(1-7) downregulated AT 1 R mRNA, upregulated mRNA levels of Ang II type 2 receptor (AT 2 R) and Mas receptor (MasR) and p38-MAPK phosphorylation and suppressed H22 cell-endothelial cell communication. Thus, Ang-(1-7) administration suppresses hepatocellular carcinoma via complex interactions of AT 1 R, AT 2 R and MasR and may provide a novel and promising approach for the treatment of hepatocellular carcinoma.

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“…PlGF is primarily secreted by FLSs in RA synovial tissue (6), and its production can be induced by hypoxia (14,37), cytokine stimulation (14), and a cell-to-cell contact with mesenchymal stem cells (14). Because RA joints are in a hypoxic condition, our recent findings on involvement of HIF-1a in the upregulation of PlGF expression through chromatin remodeling is particularly relevant to RA (37). In the present study, we identified that PlGF-1 and PlGF-2 are the major PlGF isoforms in FLSs.…”

Section: Discussionmentioning

confidence: 99%

Placental Growth Factor-1 and -2 Induce Hyperplasia and Invasiveness of Primary Rheumatoid Synoviocytes

Yoo

Park

Hwang

et al. 2015

The Journal of Immunology

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Inflammation-mediated oncogenesis has been implicated in a variety of cancer types. Rheumatoid synovial tissues can be viewed as a tumor-like mass, consisting of hyperplastic fibroblast-like synoviocytes (FLSs). FLSs of rheumatoid arthritis (RA) patients have promigratory and invasive characteristics, which may be caused by chronic exposure to genotoxic stimuli, including hypoxia and growth factors. We tested whether a transformed phenotype of RA-FLSs is associated with placental growth factor (PlGF), a representative angiogenic growth factor induced by hypoxia. In this study, we identified PlGF-1 and PlGF-2 as the major PlGF isoforms in RA-FLSs. Global gene expression profiling revealed that cell proliferation, apoptosis, angiogenesis, and cell migration were mainly represented by differentially expressed genes in RA-FLSs transfected with small interfering RNA for PlGF. Indeed, PlGF-deficient RA-FLSs showed a decrease in cell proliferation, migration, and invasion, but an increase in apoptotic death in vitro. PlGF gene overexpression resulted in the opposite effects. Moreover, exogeneous PlGF-1 and PlGF-2 increased survival, migration, and invasiveness of RA-FLSs by binding their receptors, Flt-1 and neuropilin-1, and upregulating the expression of antiapoptotic molecules, pErk and Bcl2. Knockdown of PlGF transcripts reduced RA-FLS proliferation in a xenotransplantation model. Collectively, in addition to their role for neovascularization, PlGF-1 and -2 promote proliferation, survival, migration, and invasion of RA-FLSs in an autocrine and paracrine manner. These results demonstrated how primary cells of mesenchymal origin acquired an aggressive and transformed phenotype. PlGF and its receptors thus offer new targets for anti-FLS therapy.

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Epigenetic control of hypoxia inducible factor-1α-dependent expression of placental growth factor in hypoxic conditions

Abstract: (2014) Epigenetic control of hypoxia inducible factor-1α-dependent expression of placental growth factor in hypoxic conditions, Epigenetics, 9:4, 600-610,

Cited by 35 publications

References 59 publications

Epigenetic Programming of Cardiovascular Disease by Perinatal Hypoxia and Fetal Growth Restriction

Epigenetic Programming of Cardiovascular Disease by Perinatal Hypoxia and Fetal Growth Restriction

Angiotensin-(1–1) Suppresses Hepatocellular Carcinoma Growth and Angiogenesis via Complex Interactions of Angiotensin II Type 1 Receptor, Angiotensin II Type 2 Receptor and Mas Receptor

Placental Growth Factor-1 and -2 Induce Hyperplasia and Invasiveness of Primary Rheumatoid Synoviocytes

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