Hypoxia‐inducible factor‐1α induces cell cycle arrest of endothelial cells

Iida, Takeshi; Mine, Shinichiro; Fujimoto, Hiroko; Suzuki, Koji; Minami, Yasuhiro; Tanaka, Yoshiya

doi:10.1046/j.1356-9597.2001.00512.x

Cited by 65 publications

(37 citation statements)

References 30 publications

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“…Decreased proliferation with HIF-1a knockdown could be related to its secondary effect in knocking down HIF-2a expression as well. A lesser role for HIF-1a in endothelial proliferation could be attributed to its ability to induce cell-cycle arrest (26)(27)(28) or to the inhibition of transcriptional activity by minichromosome maintenance proteins (29). Our results on the effects of HIF-1a on HPAEC proliferation are at variance with a report showing increased proliferation with HIF-1a overexpression (30).…”

Section: Discussioncontrasting

confidence: 57%

Differential Regulation of Pulmonary Vascular Cell Growth by Hypoxia-Inducible Transcription Factor–1α and Hypoxia-Inducible Transcription Factor–2α

Ahmad

Ahmad²,

Malcolm³

et al. 2013

Am J Respir Cell Mol Biol

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Hypoxia-inducible transcription factors HIF-1a and HIF-2a can contribute to pulmonary hypertension and vascular remodeling, but their mechanisms remain unknown. This study investigated the role of HIF-1a and HIF-2a in pulmonary artery endothelial and smooth muscle cells. The exposure of human pulmonary artery endothelial cells (HPAECs) to hypoxia (10% O 2 or 5% O 2 ) increased proliferation over 48 hours, compared with cells during normoxia (21% O 2 ). The adenovirus-mediated overexpression of HIF-2a that is transcriptionally active during normoxia (mutHIF-2a) increased HPAEC proliferation, whereas the overexpression of HIF-1a, which is transcriptionally active during normoxia (mutHIF-1a), exerted no effect. The knockdown of HIF-2a decreased proliferation during both hypoxia and normoxia. Both HIFs increased migration toward fibrinogen, used as a chemoattractant. In an angiogenesis tube formation assay, mutHIF-2a-transduced cells demonstrated increased tube formation, compared with the mutHIF-1a-transduced cells. In addition, the tubes formed in HIF-2a-transduced cells were more enduring than those in the other groups. In human pulmonary artery smooth muscle cells (HPASMCs), chronic exposure to hypoxia increased proliferation, compared with cells during normoxia. For HPASMCs transduced with adenoviral HIFs, HIF-1a increased proliferation, whereas HIF-2a exerted no such effect. Thus, HIF-1a and HIF-2a exert differential effects in isolated cells of the human pulmonary vasculature. This study demonstrates that HIF-2a plays a predominant role in the endothelial growth pertinent to the remodeling process. In contrast, HIF-1a appears to play a major role in pulmonary smooth muscle growth. The selective targeting of each HIF in specific target cells may more effectively counteract hypoxic pulmonary hypertension and vascular remodeling.

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Section: Discussioncontrasting

confidence: 57%

Differential Regulation of Pulmonary Vascular Cell Growth by Hypoxia-Inducible Transcription Factor–1α and Hypoxia-Inducible Transcription Factor–2α

Ahmad

Ahmad²,

Malcolm³

et al. 2013

Am J Respir Cell Mol Biol

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“…Our experimental results are contradictory with some other investigations (15,16,22,23), one possible reason is that we deployed a new experimental platform in which HIF-1α can be stably expressed. In the current study, we used a Tet-on inducible system to regulate HIF-1α expression in vitro.…”

Section: Distribution Of Cell Cycle (contrasting

confidence: 54%

“…Unfortunately, they do not reach a consensus. On the issue of relationship between HIF-1α and tumor cell proliferation, some researchers believed that high expression of HIF-1α would impede tumor cell cycle and inhibit cell proliferation (15,16), but others reached exactly the opposite results (17,18). Whether HIF-1α expression induce tumor cell apoptosis or not, different studies have varying conclusions.…”

Section: Introductionmentioning

confidence: 99%

Role of hypoxia-inducible-1α in hepatocellular carcinoma cells using a Tet-on inducible system to regulate its expression inï¿½vitro

Liu²,

Peng³

et al. 2011

Oncol Rep

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Abstract. Hypoxia-inducible-1α (HIF-1α) expression was intimately correlated with apoptosis and proliferation of cancer cells. However, conclusions of different studies on the effects of HIF-1α expression on cell apoptosis and cell proliferation of hepatoma cells remain controversial. In view of the current status, we reassess its roles and possible mechanism in hepatoma cells. In order to acquire more convincing and reliable results, we used a Tet-on system to stably and effectively regulate HIF-1α expression in the HepG2 cells in vitro. In our study we not only confirmed some common conclusions of previous studies, but also acquired some different and significant results that HIF-1α facilitates cell proliferation and cell cycle through influencing the expression of cyclin A and cyclin D, and suppresses cell apoptosis through inducing the expression of survivin and Bcl-2. These results further enrich our knowledge on the role of HIF-1α expression on cell apoptosis and cell proliferation of hepatoma cells.

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“…In contrast, in rabbits treated with MPSLþBMT, these haematological data were restored to normal levels. There have been reports that steroids and hypoxia-inducible factor-1 induce cell cycle arrest of endothelial cells, which regulate the blood coagulating system and fibrinolytic system [30,31]. Therefore, we suggest that the damaged endothelial cells cause deregulation of the blood coagulating system and fibrinolytic system.…”

Section: Discussionmentioning

confidence: 91%

Prevention of corticosteroid-induced osteonecrosis in rabbits by intra-bone marrow injection of autologous bone marrow cells

et al. 2008

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Objectives. Femoral head osteonecrosis (ON) is a serious complication of steroid administration. We evaluated bone marrow transplantation (BMT) for preventing corticosteroid-induced ON. Methods. Rabbits, injected with methylprednisolone (MPSL; 20 mg/kg), were divided into four groups: (i) MPSL alone; MPSL injection only, (ii) MPSLþneedling; 2 days after MPSL injection, a hole (1.2 mm diameter) was drilled from the outer cortex 2.5 cm distal to the proximal end of the greater trochanter, (iii) MPSLþsaline; 2 days after MPSL injection, 2 ml saline was injected directly into the bone marrow cavity, and (iv) MPSLþBMT; 2 days after MPSL injection, 1 Â 10 7 /2 ml bone marrow cells (BMCs) were injected directly into the bone marrow cavity. Platelets, fibrinogen, prothrombin time and total cholesterol in peripheral blood were measured before and after treatment. Tissues were stained with haematoxylin and eosion and terminal deoxynucleotidyl-mediated deoxyuridine triphosphate nick-end labelling stain and immunostained for VEGF, while cell proliferation and viability of whole BMCs in the femur were analysed by cell cycle analysis and [ 3 H]-thymidine uptake.Results. The ON incidence in rabbits treated with MPSL alone, MPSLþneedling and MPSLþsaline was 72.7, 70.0 and 66.7%, respectively, while in the MPSLþBMT group, the incidence was 0%. Serological findings in the MPSLþBMT group were almost normalized. VEGF and TUNEL staining were reduced in the MPSLþBMT group compared with all other groups. There were significantly fewer BMCs in G1 phase from the MPSLþBMT group than the other groups, while uptake of [ 3 H]-thymidine was significantly increased. Conclusion. Direct injection of autologous BMCs into femurs prevents corticosteroid-induced ON following treatment with high-dose, short-term steroids.

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Hypoxia‐inducible factor‐1α induces cell cycle arrest of endothelial cells

Abstract: Background : Hypoxia can induce tissue injury, including apoptosis of endothelial cells. However, little is known about the effects of hypoxia on endothelial cell function. We assessed the effects of hypoxia inducible factor (HIF)-1 α α α α on the functional charac-

Cited by 65 publications

References 30 publications

Differential Regulation of Pulmonary Vascular Cell Growth by Hypoxia-Inducible Transcription Factor–1α and Hypoxia-Inducible Transcription Factor–2α

Differential Regulation of Pulmonary Vascular Cell Growth by Hypoxia-Inducible Transcription Factor–1α and Hypoxia-Inducible Transcription Factor–2α

Role of hypoxia-inducible-1α in hepatocellular carcinoma cells using a Tet-on inducible system to regulate its expression inï¿½vitro

Prevention of corticosteroid-induced osteonecrosis in rabbits by intra-bone marrow injection of autologous bone marrow cells

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