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Gene Review

Ang2  -  angiogenin, ribonuclease A family, member 2

Mus musculus

Synonyms: Angiogenin-2, Angiogenin-related protein, Angrp, Raa3, Rnase5b
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Disease relevance of Ang2


High impact information on Ang2


Chemical compound and disease context of Ang2

  • In mice with ubiquitous doxycycline-inducible expression of Ang2, in the absence of doxycycline, intravitreous injection of a gutless adenoviral vector expressing VEGF (AGV.VEGF) resulted in neovascularization of the cornea and iris, but no retinal neovascularization [4].
  • These data establish a functional link between Ang2 interaction with alpha(v)beta(1) integrin and glioma cell invasion through the FAK/p130(Cas)/ERK1/2 and JNK-mediated signaling pathway [5].

Biological context of Ang2

  • Understanding the regulation of macrophage Ang2 production is especially important in an effort to target the pathologic role of macrophages while preserving their role in immunity and homeostasis [6].
  • The mouse angiogenin gene family: structures of an angiogenin-related protein gene and two pseudogenes [7].
  • Hyperoxia induces and activates the extrinsic and mitochondrial cell death pathways and activates initiator and effector caspases through Ang2-dependent pathways in vivo [2].
  • METHODS: We examined the combination effect of VEGF and Ang-2 overexpression by means of a combination of a retroviral tetracycline (tet) regulated gene manipulating system in vivo, by providing tet in the drinking water, and a conventional plasmid gene expression system [8].
  • Ang2 showed no effect on proliferation, but stimulated chemotaxis and tube-like structure formation [9].

Anatomical context of Ang2

  • In adults, Ang1 is associated with blood vessel stabilization and recruitment of perivascular cells, whereas Ang2 acts to counter these actions [10].
  • VEGF induced both a time- and concentration-dependent increase in angiopoietin-2 (Ang2) mRNA expression in bovine microvascular endothelial cells [1].
  • The abnormal lymphatic periendothelial cells were considered to be a type of pericyte for the lymphatic capillaries after the deletion of Ang2, because they were ultrastructurally characterized by abundant thin myofilaments in their cytoplasm and long cytoplasmic extensions similar to those shown by blood vascular pericytes [11].
  • Since stimulation of the PKA pathway can lead to macrophage production of VEGF, it is possible that enhancement of Ang2 production by macrophages may be due to autocrine responsiveness to VEGF [6].
  • Ang2 expression in the highly proliferative tumor vascular endothelium was also increased, as was phosphorylated Tie2/Tek [12].

Associations of Ang2 with chemical compounds

  • Cyclic AMP-dependent protein kinase (PKA) played a major role in this enhancement since the PKA inhibitor, H89, blocked secretion of Ang2 [6].
  • The secretion of Ang2 was enhanced by treatment with lipopolysaccharide, interferon-gamma, prostaglandin E2 and other cyclic AMP-elevating agents, as well as vascular endothelial growth factor (VEGF) [6].
  • In addition, improper creation of a new cysteine in Ang2 (Ang2S263C) dramatically induced Ang2 aggregation without activating Tie2 [13].
  • Tie2 was tyrosine phoshorylated by Ang2 [9].
  • Examination of the uteri revealed Ang-2 mRNA and protein expression in the oestrogen-dominated cycling phase and the progesterone-dominated mated phase, whereas Ang-1 expression was restricted to the mated phase [14].

Other interactions of Ang2

  • In the present study, the relationship of Angrp to Ang has been investigated by producing both proteins in bacteria and comparing their functional properties [15].
  • Double-labeled immunostaining demonstrated that ZO-1-positive staining was significantly decreased on the microvessel wall in the VEGF plus Ang-2-treated group [16].
  • Furthermore, the combination of VEGF and Ang-2 may lead to BBB disruption because it increases MMP-9 activity and inhibits ZO-1 expression [16].
  • However, the function of angiopoietin-2 (Ang-2) in cerebral angiogenesis has not been clarified [16].
  • Pigment epithelium-derived factor (PEDF) was increased more than 67-fold compared to Ang-2 in resting cornea of both C57BL/6J and 129S3/SvIM strains (P < 0.0001; P < 0.0001), suggesting a strongly antiangiogenic environment [17].

Analytical, diagnostic and therapeutic context of Ang2


  1. Hypoxia and vascular endothelial growth factor selectively up-regulate angiopoietin-2 in bovine microvascular endothelial cells. Oh, H., Takagi, H., Suzuma, K., Otani, A., Matsumura, M., Honda, Y. J. Biol. Chem. (1999) [Pubmed]
  2. Hyperoxia causes angiopoietin 2-mediated acute lung injury and necrotic cell death. Bhandari, V., Choo-Wing, R., Lee, C.G., Zhu, Z., Nedrelow, J.H., Chupp, G.L., Zhang, X., Matthay, M.A., Ware, L.B., Homer, R.J., Lee, P.J., Geick, A., de Fougerolles, A.R., Elias, J.A. Nat. Med. (2006) [Pubmed]
  3. Methylglyoxal modification of mSin3A links glycolysis to angiopoietin-2 transcription. Yao, D., Taguchi, T., Matsumura, T., Pestell, R., Edelstein, D., Giardino, I., Suske, G., Ahmed, N., Thornalley, P.J., Sarthy, V.P., Hammes, H.P., Brownlee, M. Cell (2006) [Pubmed]
  4. Angiopoietin-2 enhances retinal vessel sensitivity to vascular endothelial growth factor. Oshima, Y., Deering, T., Oshima, S., Nambu, H., Reddy, P.S., Kaleko, M., Connelly, S., Hackett, S.F., Campochiaro, P.A. J. Cell. Physiol. (2004) [Pubmed]
  5. Angiopoietin 2 induces glioma cell invasion by stimulating matrix metalloprotease 2 expression through the alphavbeta1 integrin and focal adhesion kinase signaling pathway. Hu, B., Jarzynka, M.J., Guo, P., Imanishi, Y., Schlaepfer, D.D., Cheng, S.Y. Cancer Res. (2006) [Pubmed]
  6. Expression and regulation of murine macrophage angiopoietin-2. Hubbard, N.E., Lim, D., Mukutmoni, M., Cai, A., Erickson, K.L. Cell. Immunol. (2005) [Pubmed]
  7. The mouse angiogenin gene family: structures of an angiogenin-related protein gene and two pseudogenes. Brown, W.E., Nobile, V., Subramanian, V., Shapiro, R. Genomics (1995) [Pubmed]
  8. Angiopoietin 2 displays a vascular endothelial growth factor dependent synergistic effect in hepatocellular carcinoma development in mice. Yoshiji, H., Kuriyama, S., Noguchi, R., Yoshii, J., Ikenaka, Y., Yanase, K., Namisaki, T., Kitade, M., Uemura, M., Masaki, T., Fukui, H. Gut (2005) [Pubmed]
  9. Angiopoietin 2 stimulates migration and tube-like structure formation of murine brain capillary endothelial cells through c-Fes and c-Fyn. Mochizuki, Y., Nakamura, T., Kanetake, H., Kanda, S. J. Cell. Sci. (2002) [Pubmed]
  10. Angiopoietin-1 promotes lymphatic sprouting and hyperplasia. Tammela, T., Saaristo, A., Lohela, M., Morisada, T., Tornberg, J., Norrmén, C., Oike, Y., Pajusola, K., Thurston, G., Suda, T., Yla-Herttuala, S., Alitalo, K. Blood (2005) [Pubmed]
  11. Abnormal recruitment of periendothelial cells to lymphatic capillaries in digestive organs of angiopoietin-2-deficient mice. Shimoda, H., Bernas, M.J., Witte, M.H., Gale, N.W., Yancopoulos, G.D., Kato, S. Cell Tissue Res. (2007) [Pubmed]
  12. Expression and hypoxic regulation of angiopoietins in human astrocytomas. Ding, H., Roncari, L., Wu, X., Lau, N., Shannon, P., Nagy, A., Guha, A. Neuro-oncology (2001) [Pubmed]
  13. Oligomerization and multimerization are critical for angiopoietin-1 to bind and phosphorylate Tie2. Kim, K.T., Choi, H.H., Steinmetz, M.O., Maco, B., Kammerer, R.A., Ahn, S.Y., Kim, H.Z., Lee, G.M., Koh, G.Y. J. Biol. Chem. (2005) [Pubmed]
  14. Angiopoietin-1 and -2 mRNA and protein expression in mouse preimplantation embryos and uteri suggests a role in angiogenesis during implantation. Hess, A.P., Hirchenhain, J., Schanz, A., Talbi, S., Hamilton, A.E., Giudice, L.C., Krüssel, J.S. Reprod. Fertil. Dev. (2006) [Pubmed]
  15. Characterization of mouse angiogenin-related protein: implications for functional studies on angiogenin. Nobile, V., Vallee, B.L., Shapiro, R. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  16. Angiopoietin-2 facilitates vascular endothelial growth factor-induced angiogenesis in the mature mouse brain. Zhu, Y., Lee, C., Shen, F., Du, R., Young, W.L., Yang, G.Y. Stroke (2005) [Pubmed]
  17. Mouse strain-dependent heterogeneity of resting limbal vasculature. Chan, C.K., Pham, L.N., Chinn, C., Spee, C., Ryan, S.J., Akhurst, R.J., Hinton, D.R. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  18. Sustained angiopoietin-2 expression disrupts vessel formation and inhibits glioma growth. Lee, O.H., Fueyo, J., Xu, J., Yung, W.K., Lemoine, M.G., Lang, F.F., Bekele, B.N., Zhou, X., Alonso, M.A., Aldape, K.D., Fuller, G.N., Gomez-Manzano, C. Neoplasia (2006) [Pubmed]
  19. Vascular endothelial growth factor-A, vascular endothelial growth factor receptor-2 and angiopoietin-2 expression in the mouse choroid plexuses. Nico, B., Mangieri, D., Corsi, P., De Giorgis, M., Vacca, A., Roncali, L., Ribatti, D. Brain Res. (2004) [Pubmed]
  20. A single local injection of recombinant VEGF receptor 2 but not of Tie2 inhibits retinal neovascularization in the mouse. Agostini, H., Boden, K., Unsöld, A., Martin, G., Hansen, L., Fiedler, U., Esser, N., Marmé, D. Curr. Eye Res. (2005) [Pubmed]
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