Adrenomedullin promotes human endothelial cell proliferation via HIF-1α

Chen, Li; Qiu, Juhui; Zhang, Lingling; Luo, Xiangdong

doi:10.1007/s11010-012-1267-1

Cited by 25 publications

(17 citation statements)

References 32 publications

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“…1 ) β-Adrenergic stimulation induces the production of mitochondrial ROS in brown adipocytes 24 . 2 ) Cold-stimulated mitochondrial uncoupling induces hypoxia in BAT 41 . 3 ) FCCP-induced mitochondrial uncoupling decreases mitochondrial ROS production in brown adipocytes 42, 43 .…”

Section: Discussionmentioning

confidence: 99%

Regulation of glycolysis in brown adipocytes by HIF-1α

Basse

Isidor

Winther

et al. 2017

Sci Rep

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Brown adipose tissue takes up large amounts of glucose during cold exposure in mice and humans. Here we report an induction of glucose transporter 1 expression and increased expression of several glycolytic enzymes in brown adipose tissue from cold-exposed mice. Accordingly, these genes were also induced after β-adrenergic activation of cultured brown adipocytes, concomitant with accumulation of hypoxia inducible factor-1α (HIF-1α) protein levels. HIF-1α accumulation was dependent on uncoupling protein 1 and generation of mitochondrial reactive oxygen species. Expression of key glycolytic enzymes was reduced after knockdown of HIF-1α in mature brown adipocytes. Glucose consumption, lactate export and glycolytic capacity were reduced in brown adipocytes depleted of Hif-1α. Finally, we observed a decreased β-adrenergically induced oxygen consumption in Hif-1α knockdown adipocytes cultured in medium with glucose as the only exogenously added fuel. These data suggest that HIF-1α-dependent regulation of glycolysis is necessary for maximum glucose metabolism in brown adipocytes.

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Section: Discussionmentioning

confidence: 99%

Regulation of glycolysis in brown adipocytes by HIF-1α

Basse

Isidor

Winther

et al. 2017

Sci Rep

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“…This observation indicates that the accumulation of HIF-1α may upregulate ADM mRNA expression, which may enhance the synthesis and secretion of ADM in endothelial and smooth muscle cells. In response to prolonged hypoxia, vascular remodeling and endothelial injury occur and the activity of the endothelium-derived vasodilator pathway decreases, resulting in a gradual decrease in ADM synthesis and suppression of the effects of ADM on vascular smooth muscle cell proliferation (21). Finally, the potent vasoconstriction and cell proliferation promoted by ET-1 lead to an imbalance between vasoconstrictors and vasodilators, resulting in the development of vascular remodeling and pulmonary hypertension (22).…”

Section: Discussionmentioning

confidence: 99%

Expression of hypoxia-inducible factor-1α, endothelin-1 and adrenomedullin in newborn rats with hypoxia-induced pulmonary hypertension

Wang

Zhou

et al. 2014

Experimental and Therapeutic Medicine

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Hypoxia-inducible factor (HIF)-1α is associated with hypoxia-induced pulmonary hypertension (HPH) in adults. In the present study, the expression levels of HIF-1α, endothelin (ET)-1 and adrenomedullin (ADM) were analyzed during HPH in neonates. In total, 96 newborn rats were subjected to hypoxia or normoxia for 3, 5, 7, 10, 14 or 21 days (n=8 per subgroup). HIF-1α, ET-1 and ADM expression levels were measured by quantitative polymerase chain reaction. In addition, the intima-media thickness/external diameter ratio (MT%) and medial wall cross-sectional area/vessel total cross-sectional area ratio (MA%) were calculated to evaluate pulmonary vascular remodeling. The mean pulmonary arterial pressure (mPAP) increased with exposure to hypoxia. Furthermore, the expression levels of HIF-1α, ET-1 and ADM in the lungs were shown to increase after three and five days of hypoxia, while the MT% and MA% increased after seven days of hypoxia, as compared with the controls (P<0.05). Therefore, the expression of HIF-1α, ET-1 and ADM is upregulated in the lungs of newborn rats during early HPH. At later stages, the mPAP increases, vascular remodeling occurs and HIF-1α, ET-1 and ADM expression levels restore to normal levels.

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“…Adrenomedullin (ADM) is a vascular-derived peptide that was initially purified from a phaeochromocytoma (14) but has also been shown to be expressed in other body tissues, suggesting that it possesses numerous biological functions. In addition to being produced by both stromal (i.e., endothelial, vascular smooth muscle, myocardial and central nervous system) and tumor cells, as an autocrine/paracrine factor, ADM has been shown to be produced during the differentiation of macrophages in response to pro-inflammatory stimuli and hypoxia (15,16). ADM is also implicated in renal fibrogenesis, and the expression of ADM and its receptor, in rat kidney interstitial cells, has been shown to inhibit cell proliferation and mRNA expression levels of ECM proteins (17).…”

Section: Hypoxia-inducible Adrenomedullin Ameliorates the Epithelial-mentioning

confidence: 99%

Hypoxia-inducible adrenomedullin ameliorates the epithelial-to-mesenchymal transition in human proximal tubular epithelial cells

Zhu

Yang

Liu

et al. 2015

Molecular Medicine Reports

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Renal tubular epithelial cells can enter the epithelial‑to‑mesenchymal transition (EMT) in response to chronic hypoxia. EMT is a process which involves the phenotypic conversion of epithelial cells, that is believed to have an important role in renal fibrosis. However, the underlying mechanisms of the involvement of EMT in renal fibrosis remain to be elucidated. Adrenomedullin (AMD) has been implicated in renal fibrosis and is induced by hypoxia. The aims of the present study were to determine whether ADM signaling was active in human proximal tubular epithelial cells cultured under hypoxic conditions, and to observe the activity of ADM during EMT. The expression levels of ADM were significantly increased, in a time‑dependent manner, in HK‑2 and HKC human proximal tubular epithelial cells, cultured under hypoxic conditions. Overexpression of exogenous ADM was accompanied by increased expression levels of the epithelial markers E‑cadherin and tight junction protein‑1, and decreased expression levels of the mesenchymal markers vimentin and α‑smooth muscle actin, during hypoxia. Knock‑down of ADM expression by small hairpin RNA, or co‑administration of an ADM peptide inhibitor, in HK‑2 cells significantly exacerbated hypoxia‑induced EMT, as compared to the lack of effect observed in the untransfected controls. ADM was shown to suppress EMT by inhibiting the activation of extracellular signal‑regulated kinase (ERK), and this effect was prevented by the ERK activator apigenin. The results of the present study suggest that ADM has an important role in promoting EMT in hypoxic human proximal tubular epithelial cells. ADM may therefore represent a novel therapeutic target in the treatment of injured kidneys.

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Adrenomedullin promotes human endothelial cell proliferation via HIF-1α

Cited by 25 publications

References 32 publications

Regulation of glycolysis in brown adipocytes by HIF-1α

Regulation of glycolysis in brown adipocytes by HIF-1α

Expression of hypoxia-inducible factor-1α, endothelin-1 and adrenomedullin in newborn rats with hypoxia-induced pulmonary hypertension

Hypoxia-inducible adrenomedullin ameliorates the epithelial-to-mesenchymal transition in human proximal tubular epithelial cells

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