Stabilization of hepatocyte growth factor mRNA by hypoxia-inducible factor 1

Chu, Sheng-Hua; Feng, Donghan; Ma, Yupo; Zhu, Zhenan; Zhang, Hong; Qiu, Jianhua

doi:10.1007/s11033-008-9406-1

Cited by 31 publications

(24 citation statements)

References 55 publications

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“…26,35 HIF also regulates genes indirectly by interactions with other transcription factors, by stabilization of mRNAs, and by regulation of microRNAs. [35][36][37][38][39][40] Taken together, these data provide an explanation for the reduction in BMP signaling previously reported in chronically hypoxic hypertensive lungs in the absence of BMPR2 mutations. 15 Furthermore, because the hypoxic increase in gremlin 1 is restricted to the lung and is not observed in other organs, these data identify a mechanism that can account for the structural component of the increase in vascular resistance in response to sustained hypoxia, which is unique to the pulmonary circulation, such as that observed in chronic lung diseases and at high altitude.…”

Section: Discussionsupporting

confidence: 72%

Gremlin Plays a Key Role in the Pathogenesis of Pulmonary Hypertension

et al. 2012

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Background-Pulmonary hypertension occurs in chronic hypoxic lung diseases, significantly worsening morbidity and mortality. The important role of altered bone morphogenetic protein (BMP) signaling in pulmonary hypertension was first suspected after the identification of heterozygous BMP receptor mutations as the underlying defect in the rare heritable form of pulmonary arterial hypertension. Subsequently, it was demonstrated that BMP signaling was also reduced in common forms of pulmonary hypertension, including hypoxic pulmonary hypertension; however, the mechanism of this reduction has not previously been elucidated. Methods and Results-Expression of 2 BMP antagonists, gremlin 1 and gremlin 2, was higher in the lung than in other organs, and gremlin 1 was further increased in the walls of small intrapulmonary vessels of mice during the development of hypoxic pulmonary hypertension. Hypoxia stimulated gremlin secretion from human pulmonary microvascular endothelial cells in vitro, which inhibited endothelial BMP signaling and BMP-stimulated endothelial repair. Haplodeficiency of gremlin 1 augmented BMP signaling in the hypoxic mouse lung and reduced pulmonary vascular resistance by attenuating vascular remodeling. Furthermore, gremlin was increased in the walls of small intrapulmonary vessels in idiopathic pulmonary arterial hypertension and the rare heritable form of pulmonary arterial hypertension in a distribution suggesting endothelial localization. Conclusions-These findings demonstrate a central role for increased gremlin in hypoxia-induced pulmonary vascular remodeling and the increased pulmonary vascular resistance in hypoxic pulmonary hypertension. High levels of basal gremlin expression in the lung may account for the unique vulnerability of the pulmonary circulation to heterozygous mutations of BMP type 2 receptor in pulmonary arterial hypertension. (Circulation. 2012;125:920-930.)

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Section: Discussionsupporting

confidence: 72%

Gremlin Plays a Key Role in the Pathogenesis of Pulmonary Hypertension

et al. 2012

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“…Hypoxia is known to be a potent angiogenic inducer [1]. Hypoxia led to an upregulation of hypoxia-inducible factor (HIF), which moves into the nucleus where it binds to hypoxia response elements within target angiogenic growth factor genes and initiates their transcription [5,9,22]. Hypoxia also stimulates the expression of leptin and VEGF mRNA in differentiated 3T3-F442A adipocytes [25].…”

Section: Discussionmentioning

confidence: 99%

Fat Depot-Specific Differences in Angiogenic Growth Factor Gene Expression and Its Relation to Adipocyte Size in Cattle

Yamada

Kawakami

Nakanishi

2010

The Journal of Veterinary Medical Science

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ABSTRACT. Adipocytes derived from different anatomical sites vary in the expression of adipocytokines and growth factor genes. Adipogenesis is tightly associated with angiogenesis, although the regional variation of angiogenic growth factor gene expression in adipose tissues remains unclear. In this experiment, we studied the fat depot-specific differences (subcutaneous, intramuscular, intermuscular, renal, and mesenteric) in the expression of angiogenic growth factor mRNA [vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), fibroblast growth factor-10 (FGF-10), hepatocyte growth factor (HGF), and leptin], as well as the relationship between angiogenic growth factor mRNA level and adipocyte size in bovine adipose tissues. Intermuscular, renal, and mesenteric adipose tissues expressed significantly higher VEGF, FGF-2, and leptin mRNA levels than did subcutaneous and intramuscular adipose tissues. Mesenteric adipose tissue also expressed higher FGF-10 mRNA levels than did subcutaneous and intramuscular adipose tissues. There was no significant difference in the expression of HGF mRNA among adipose tissue depots. A significant correlation existed between adipocyte size and VEGF, FGF-2, FGF-10, and leptin mRNA levels. These results indicate that fat depot-specific difference in angiogenic growth factor gene expression results from the difference in adipocyte size.

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“…U251 and SHG44 cells were washed in PBS and lysed in buffer using the standard methods. 15,16 The samples of glioma tissues of nude mice in the five groups were homogenized in an RIPA lysis buffer. Lysates were cleared by centrifugation (14,000 rpm) at 4°C for 30 minutes.…”

Section: Western Blotting Analysismentioning

confidence: 99%

Hydroxyapatite nanoparticles inhibit the growth of human glioma cells in vitro and in vivo

Chu¹,

Feng²,

Ma³

et al. 2012

IJN

Self Cite

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Hydroxyapatite nanoparticles (nano-HAPs) have been reported to exhibit antitumor effects on various human cancers, but the effects of nano-HAPs on human glioma cells remain unclear. The aim of this study was to explore the inhibitory effect of nano-HAPs on the growth of human glioma U251 and SHG44 cells in vitro and in vivo. Nano-HAPs could inhibit the growth of U251 and SHG44 cells in a dose-and time-dependent manner, according to methyl thiazoletetrazolium assay and flow cytometry. Treated with 120 mg/L and 240 mg/L nano-HAPs for 48 hours, typical apoptotic morphological changes were noted under Hoechst staining and transmission electron microscopy. The tumor growth of cells was inhibited after the injection in vivo, and the related side effects significantly decreased in the nano-HAP-and-drug combination group. Because of the function of nano-HAPs, the expression of c-Met, SATB1, Ki-67, and bcl-2 protein decreased, and the expression of SLC22A18 and caspase-3 protein decreased noticeably. The findings indicate that nano-HAPs have an evident inhibitory action and induce apoptosis of human glioma cells in vitro and in vivo. In a drug combination, they can significantly reduce the adverse reaction related to the chemotherapeutic drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU).

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Stabilization of hepatocyte growth factor mRNA by hypoxia-inducible factor 1

Cited by 31 publications

References 55 publications

Gremlin Plays a Key Role in the Pathogenesis of Pulmonary Hypertension

Gremlin Plays a Key Role in the Pathogenesis of Pulmonary Hypertension

Fat Depot-Specific Differences in Angiogenic Growth Factor Gene Expression and Its Relation to Adipocyte Size in Cattle

Hydroxyapatite nanoparticles inhibit the growth of human glioma cells in vitro and in vivo

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