Hypoxic conditions stimulate the production of angiogenin and vascular endothelial growth factor by human renal proximal tubular epithelial cells in culture

Nakamura, Masayuki; Yamabe, Hideaki; Osawa, Hiroshi; Nakamura, Norio; Shimada, Michiko; Kumasaka, Ryuichiro; Murakami, Reiichi; Fujita, Takeshi; Osanai, Tomohiro; Okumura, Ken

doi:10.1093/ndt/gfl041

Cited by 71 publications

(51 citation statements)

References 16 publications

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“…According to these findings, an absolute increase in capillary density takes place in hypothyroid hearts, which may result from an increased cardiac production of angiogenic factors (bFGF and HIF-1a), as observed in bradycardia . By contrast, plasma angiogenin, one of the most potent angiogenic factors (Nakamura et al 2006), was markedly reduced in hypothyroid rats. This decrease, together with the vasoconstriction secondary to reduced metabolic needs (Liu et al 2010), may participate in reducing the number of blood vessels in the mesenteric vascular bed.…”

Section: Discussionmentioning

confidence: 78%

“…The recognised angiogenic factors (Fett et al 1985, Risau & Flamme 1995, Nakamura et al 2006) VEGF and angiogenin were measured in plasma and all these factors plus HIF-1a in the heart and kidney. Hearts and kidneys were homogenised in 50 mm HCl-Tris (pH 7.4) containing 1% Triton X-100 and centrifuged for 15 min at 1000 g. VEGF was analysed by Luminex x-MAP technology with a kit purchased from Millipore (Billerica, MA, USA), while bFGF, angiogenin and HIF-1a were measured by ELISA with kits purchased from Cusabio (Wuhan, China).…”

Section: Angiogenic Factorsmentioning

confidence: 99%

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Influence of thyroid state on cardiac and renal capillary density and glomerular morphology in rats

Rodríguez-Gómez

Banegas

Wangensteen

et al. 2012

Journal of Endocrinology

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The purpose was to analyse the cardiac and renal capillary density and glomerular morphology resulting from a chronic excess or deficiency of thyroid hormones (THs) in rats. We performed histopathological, morphometrical and immunohistochemical analyses in hypothyroid and hyperthyroid rats to evaluate the density of mesenteric, renal and cardiac vessels at 4 weeks after induction of thyroid disorders. The main angiogenic factors in plasma, heart and kidney were measured as possible mediators of vascular changes. Mesenteric vessel branching was augmented and decreased in hyper-and hypothyroid rats respectively. The numerical density of CD31-positive capillaries was higher in left and right ventricles and in cortical and medullary kidney from both hyper-and hypothyroid rats vs controls. Numbers of podocytes and glomeruli per square millimetre were similar among groups. Glomerular area and percentage mesangium were greater in the hyperthyroid vs control or hypothyroid groups. No morphological renal lesions were observed in any group. Vascularisation of the mesenteric bed is related to TH levels, but an increased capillarity was observed in heart and kidney in both thyroid disorders. This increase may be produced by higher tissue levels of angiogenic factors in hypothyroid rats, whereas haemodynamic factors would predominate in hyperthyroid rats. Our results also indicate that the renal dysfunctions of thyroid disorders are not related to cortical or medullary microvascular rarefaction and that the proteinuria of hyperthyroidism is not secondary to a podocyte deficit. Finally, TH or its analogues may be useful to increase capillarity in renal diseases associated with microvascular rarefaction.

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Section: Discussionmentioning

confidence: 78%

Section: Angiogenic Factorsmentioning

confidence: 99%

Influence of thyroid state on cardiac and renal capillary density and glomerular morphology in rats

Rodríguez-Gómez

Banegas

Wangensteen

et al. 2012

Journal of Endocrinology

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“…28,29 However, the cleavage of intact tRNA by angiogenin does not result from a simple upregulation of angiogenin ( Figure 3B). The knockout of Ang1 also did not affect the immunostaining by anti-m1A antibody in the damaged tissue ( Figure 2E).…”

Section: Conformational Change Of Trna Is a Stress Sensormentioning

confidence: 92%

Conformational Change in Transfer RNA Is an Early Indicator of Acute Cellular Damage

Mishima

Inoue

Saigusa³

et al. 2014

Journal of the American Society of Nephrology

104

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Tissue damage by oxidative stress is a key pathogenic mechanism in various diseases, including AKI and CKD. Thus, early detection of oxidative tissue damage is important. Using a tRNA-specific modified nucleoside 1-methyladenosine (m1A) antibody, we show that oxidative stress induces a direct conformational change in tRNA structure that promotes subsequent tRNA fragmentation and occurs much earlier than DNA damage. In various models of tissue damage (ischemic reperfusion, toxic injury, and irradiation), the levels of circulating tRNA derivatives increased rapidly. In humans, the levels of circulating tRNA derivatives also increased under conditions of acute renal ischemia, even before levels of other known tissue damage markers increased. Notably, the level of circulating free m1A correlated with mortality in the general population (n=1033) over a mean follow-up of 6.7 years. Compared with healthy controls, patients with CKD had higher levels of circulating free m1A, which were reduced by treatment with pitavastatin (2 mg/d; n=29). Therefore, tRNA damage reflects early oxidative stress damage, and detection of tRNA damage may be a useful tool for identifying organ damage and forming a clinical prognosis.

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“…However, it has been shown that accumulation of ANG in the nucleolus of target endothelial cells is essential for its biological activity (23,24) and that ANG binds to a receptor on the surface of endothelial cells (25,26) and induces a variety of activities required for angiogenesis (26)(27)(28). ANG has been shown to be upregulated by hypoxia in cultured melanoma cells (29) and in human renal proximal tubular epithelial cells (30).…”

mentioning

confidence: 99%

Characterization of Human Angiogenin Variants Implicated in Amyotrophic Lateral Sclerosis

et al. 2007

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Human angiogenin (ANG), the first member of the angiogenin family (from the pancreatic ribonuclease A superfamily) to be identified, is an angiogenic factor that induces neovascularization. It has received much attention due to its involvement in the growth of tumors and its elevated expression level in pancreatic and several other cancers. Recently the biological role of ANG has been shown to extend to the nervous system. Mutations in ANG have been linked with familial as well as sporadic forms of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder characterized by selective destruction of motor neurons. Furthermore, mouse angiogenin-1 has been shown to be expressed in the developing nervous system and during the neuronal differentiation of pluripotent stem cells. We have now characterized the seven variants of ANG reported in ALS patients with respect to the known biochemical properties of ANG and further studied the biological properties of three of these variants. Our results show that the ribonucleolytic activity of six of the seven ANG-ALS implicated variants is significantly reduced or lost and some variants also show altered thermal stability. We report a significant reduction in the cell proliferative and angiogenic activities of the three variants that we chose to investigate further. Our studies on the biochemical and structural features of these ANG variants now form the basis for further investigations to determine their role(s) in ALS.Amyotrophic lateral sclerosis (ALS) 1 is a fatal neurodegenerative disorder characterized by selective destruction of motor neurons (1). In the past decade, a small number of genes involved in the etiology of the disease have been identified (for a recent review see ref 2). The best studied of these is SOD1 (3), the gene for Cu/Zn superoxide dismutase. More than a hundred SOD1 mutations have now been linked with ALS, and motor neuron death from many of these mutations has been shown to result from a toxic gain of function rather than loss of dismutase activity. However, mutations in SOD1 account for only 1-2% of all cases of ALS and 20% of the familial cases. Some of the other proteins implicated in ALS are the vesicle-trafficking protein VAPB (4); ALSIN, a putative guanine nucleotide factor for GTPase (5); and senataxin (6). In addition, vascular endothelial growth factor (VEGF), an angiogenic factor that plays an important role in motor neuron survival, has been linked with ALS (7-10). However, the causes and molecular mechanisms underlying ALS are still largely unclear, and effective therapies do not appear to be imminent. Angiogenin (ANG), which encodes an angiogenic protein, was recently identified as a candidate susceptibility gene for ALS in the Irish and Scottish population by Greenway et al. (11). In a further study of over 2500 individuals from five independent populations from northern Europe and North America, Greenway et al. (12) found seven missense mutations (Figure 1) in 11 unrelated individuals with sporadic ALS and in f...

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Hypoxic conditions stimulate the production of angiogenin and vascular endothelial growth factor by human renal proximal tubular epithelial cells in culture

Abstract: Under hypoxic conditions, the ANG and VEGF secreted by PTEC may modulate angiogenesis and vascular remodeling in the renal interstitium via an increase in the production of HIF-1.

Cited by 71 publications

References 16 publications

Influence of thyroid state on cardiac and renal capillary density and glomerular morphology in rats

Influence of thyroid state on cardiac and renal capillary density and glomerular morphology in rats

Conformational Change in Transfer RNA Is an Early Indicator of Acute Cellular Damage

Characterization of Human Angiogenin Variants Implicated in Amyotrophic Lateral Sclerosis

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