Endogenous angiogenin in endothelial cells is a general requirement for cell proliferation and angiogenesis

Kishimoto, Kenji; Liu, Shumei; Tsuji, Takanori; Olson, Karen A.; Hu, Guobin

doi:10.1038/sj.onc.1208223

Cited by 281 publications

(310 citation statements)

References 40 publications

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“…The yolk sac offers particular advantages for the expression analysis of vasculogenic/angiogenic and hematopoietic genes because (i) it represents a major organ of vasculature and blood development during early embryogenesis (19); (ii) its organization is relatively simpler than the embryo proper (19); and (iii) apart from the vascular defects, the size and appearance of the Hypb −/− yolk sacs were not significantly affected by the growth retardation of the embryos at the stages analyzed. Among the altered genes, notably, a potent inducer of angiogenesis namely angiogenin (Ang) was consistently down-regulated by the Hypb disruption even at early developmental stages when the phenotypes had not been visible, which would arrest the normal angiogenesis induced by other angiogenic proteins such as FGFs, epidermal growth factor (EGF), and VEGF (27). Another significantly downregulated gene Gja4 encodes the gap junction protein α4 (also known as Connexin37).…”

Section: Discussionmentioning

confidence: 99%

Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling

Sun

Zhang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

142

129

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HYPB is a human histone H3 lysine 36 (H3K36)-specific methyltransferase and acts as the ortholog of yeast Set2. This study explored the physiological function of mammalian HYPB using knockout mice. Homozygous disruption of Hypb impaired H3K36 trimethylation but not mono-or dimethylation, and resulted in embryonic lethality at E10.5-E11.5. Severe vascular defects were observed in the Hypb −/− embryo, yolk sac, and placenta. The abnormally dilated capillaries in mutant embryos and yolk sacs could not be remodeled into large blood vessels or intricate networks, and the aberrantly rounded mesodermal cells exhibited weakened interaction with endothelial cells. The embryonic vessels failed to invade the labyrinthine layer of placenta, which impaired the embryonic-maternal vascular connection. These defects could not be rescued by wildtype tetraploid blastocysts, excluding the possibility that they were caused by the extraembryonic tissues. Consistent with these phenotypes, gene expression profiling in wild-type and Hypb −/− yolk sacs revealed that the Hypb disruption altered the expression of some genes involved in vascular remodeling. At the cellular level, Hypb −/− embryonic stem cell-derived embryonic bodies, as well as in vitro-cultured human endothelial cells with siRNA-mediated suppression of HYPB, showed obvious defects in cell migration and invasion during vessel formation, suggesting an intrinsic role of Hypb in vascular development. Taken together, these results indicate that Hypb is required for embryonic vascular remodeling and provide a tool to study the function of H3K36 methylation in vasculogenesis/angiogenesis. knockout mice | embryonic lethality | vasculogenesis | angiogenesis | capillary tubule formation

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Section: Discussionmentioning

confidence: 99%

Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling

Sun

Zhang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

142

129

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“…Here, it binds to DNA (23) and stimulates the transcription and/or processing of pro-ribosomal RNA (24), thereby participating in the increased production of ribosomes essential for cell proliferation. Indeed, the presence of Ang is required for cell proliferation induced by other angiogenic factors, such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (25). The enzymatic activity of Ang, albeit several orders of magnitude lower than that of RNase A toward conventional RNase substrates (26,27), is also essential to the angiogenic process (28).…”

mentioning

confidence: 99%

Biological and Structural Features of Murine Angiogenin-4, an Angiogenic Protein^,

et al. 2007

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Murine angiogenin-4 (mAng-4) is a member of the pancreatic ribonuclease superfamily that is expressed in some endodermally derived organs. We now show that mAng-4 is angiogenic using a thoracic aorta assay never before applied to the angiogenins. mAng-4, human angiogenin (hAng), and murine angiogenin-1 (mAng-1) stimulate the proliferation of IGR1 melanoma cells but do not stimulate the proliferation or migration of bovine corneal endothelial cells or primary mouse embryonic fibroblasts. In addition, we report the 3-D structure of mAng-4 at 2.02-Å resolution. The structure shows that the residues forming the putative B 1 , P 1 , and B 2 RNA-binding subsites occupy positions similar to their hAng counterparts. The B 1 subsite is obstructed by Glu115 and Ile118. The obstruction is stabilized by a novel salt bridge between the C-terminal carboxyl group and the side chain of Arg99. Through mutational studies, we identify residues critical to the angiogenic function of mAng-4. The effect of H12A and H112A mutations in the catalytic site indicates that ribonucleolytic activity is essential to angiogenesis. The consequences of a nearby E115A mutation are consistent with a significant role for Glu115 in the attenuation of enzymatic activity but also suggest that sufficient suppression of catalysis is necessary for angiogenesis. The effect of an R32A mutation in the putative nuclear localization sequence indicates that this residue is crucial for angiogenesis. In the putative cell-binding segment, the replacement of Lys59 with Asn (its counterpart at position 61 of hAng) does not abrogate enzymatic activity but abolishes angiogenic activity, the reason for which is unclear.

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“…Endogenous angiogenin in endothelial cells is related to cell proliferation and angiogenesis [22]. HUVEC cultured in serum-free medium do not divide spontaneously but can be induced to proliferate by adding angiogenin or other angiogenic factors [22]. We actually detected 156Ϯ38 pg/ml/10 5 cells of angiogenin by ELISA in the conditioned medium from HUVEC after 48-hour culture.…”

Section: Effect Of 1 and 2 On Tube Formation Of Huvecmentioning

confidence: 85%

“…It is known that angiogenin is secreted from human cancer cells and human normal cells [10]. Endogenous angiogenin in endothelial cells is related to cell proliferation and angiogenesis [22]. HUVEC cultured in serum-free medium do not divide spontaneously but can be induced to proliferate by adding angiogenin or other angiogenic factors [22].…”

Section: Effect Of 1 and 2 On Tube Formation Of Huvecmentioning

confidence: 99%

A New Terrein Glucoside, a Novel Inhibitor of Angiogenin Secretion in Tumor Angiogenesis

et al. 2008

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Angiogenesis is a critical step for the tumor therapy. Many angiogenic factors are involved in the tumor angiogenesis. In the course of our screening for inhibitors of angiogenin secretion, one of angiogenic factors, we have isolated a new terrein glucoside (1) and terrein (2) from the fermentation broth of fungal strain Aspergillus sp. PF1381. The structure and absolute stereochemistry of 1 was determined to be (4S,5R)-5-[(a -D-glucopyranosyl)oxy]-4-hydroxy-3-(E-1-propenyl)-2-cyclopenten-1-one on the basis of spectral and enzymatic analyses. Compounds 1 and 2 equally inhibited angiogenin secretion from androgendependent prostate cancer cells, LNCaP-CR, with IC 50 values of 13 mM. However, both compounds did not affect VEGF secretion, another angiogenic factor. Furthermore, both compounds inhibited tube formation of human umbilical vein endothelial cells (HUVEC). These results suggested that 1 and 2 act as angiogenesis inhibitors through the inhibition of angiogenin secretion.

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Endogenous angiogenin in endothelial cells is a general requirement for cell proliferation and angiogenesis

Cited by 281 publications

References 40 publications

Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling

Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling

Biological and Structural Features of Murine Angiogenin-4, an Angiogenic Protein^,

A New Terrein Glucoside, a Novel Inhibitor of Angiogenin Secretion in Tumor Angiogenesis

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Endogenous angiogenin in endothelial cells is a general requirement for cell proliferation and angiogenesis

Cited by 281 publications

References 40 publications

Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling

Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling

Biological and Structural Features of Murine Angiogenin-4, an Angiogenic Protein,

A New Terrein Glucoside, a Novel Inhibitor of Angiogenin Secretion in Tumor Angiogenesis

Contact Info

Product

Resources

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Biological and Structural Features of Murine Angiogenin-4, an Angiogenic Protein^,