Akt1-dependent expression of angiopoietin 1 and 2 in vascular smooth muscle cells leads to vascular stabilization
2
조회
0
다운로드
0
인용
0
참고문헌
초록
Retinal angiogenesis was delayed in VSMC-specific Akt1-deficient mice (Akt1∆SMC) but not in Akt2∆SMC mice. The proliferation of ECs, recruitment of pericytes, and coverage of VSMCs to the endothelium were defective in Akt1∆SMC. The silencing of Akt1 in VSMCs led to the downregulation of angiopoietin 1 (Ang1) and the upregulation of Ang2. The activation of Notch3 in VSMCs was significantly reduced in the retinas of Akt1∆SMC mice. Silencing Akt1 suppressed the activation of Notch3. Moreover, the silencing of Notch3 downregulated Ang1, whereas the overexpression of Notch3 intracellular domain (NICD3) enhanced Ang1 expression. The nuclear localization and transcriptional activity of yes-associated protein (YAP) were affected by the expression level of Akt1. Silencing YAP downregulated Ang2 expression, whereas overexpression of YAP showed the opposite results. Ang1 antibody and Ang2 suppressed endothelial sprouting of wild-type aortic tissues, whereas the Ang2 antibody and Ang1 facilitated the endothelial sprouting of aortic tissues from Akt1∆SMC mice. Finally, severe hemorrhage was observed in Akt1∆SMC mice, which was further facilitated under streptozotocin (STZ)-induced diabetic conditions. Therefore, the Akt1-Notch3/YAP-Ang1/2 signaling cascade in VSMCs might play an essential role in the paracrine regulation of endothelial function.
Abstract
Retinal angiogenesis was delayed in VSMC-specific Akt1-deficient mice (Akt1∆SMC) but not in Akt2∆SMC mice. The proliferation of ECs, recruitment of pericytes, and coverage of VSMCs to the endothelium were defective in Akt1∆SMC. The silencing of Akt1 in VSMCs led to the downregulation of angiopoietin 1 (Ang1) and the upregulation of Ang2. The activation of Notch3 in VSMCs was significantly reduced in the retinas of Akt1∆SMC mice. Silencing Akt1 suppressed the activation of Notch3. Moreover, the silencing of Notch3 downregulated Ang1, whereas the overexpression of Notch3 intracellular domain (NICD3) enhanced Ang1 expression. The nuclear localization and transcriptional activity of yes-associated protein (YAP) were affected by the expression level of Akt1. Silencing YAP downregulated Ang2 expression, whereas overexpression of YAP showed the opposite results. Ang1 antibody and Ang2 suppressed endothelial sprouting of wild-type aortic tissues, whereas the Ang2 antibody and Ang1 facilitated the endothelial sprouting of aortic tissues from Akt1∆SMC mice. Finally, severe hemorrhage was observed in Akt1∆SMC mice, which was further facilitated under streptozotocin (STZ)-induced diabetic conditions. Therefore, the Akt1-Notch3/YAP-Ang1/2 signaling cascade in VSMCs might play an essential role in the paracrine regulation of endothelial function.
참고문헌 (53)
- Lee, M. Y., "Endothelial Akt1 mediates angiogenesis by phosphorylating multiple angiogenic substrates", Proc. Natl Acad. Sci. USA, 111, pp.12865~12870 (2014)
- Brazil, D. P., "Advances in protein kinase B signalling : AKTion on multiple fronts", Trends Biochem. Sci, 29, pp.233~242 (2004)
- Cho, H., "Akt1", PKBalpha is required for normal growth but dispensable for maintenance of glucose homeostasis in mice, 2001, pp.276, 38349~38352
- Cho, H., "Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2(PKB beta)", Science, 292, pp.1728~1731 (2001)
- Easton, R. M., "Role for Akt3", protein kinase Bgamma in attainment of normal brain size, 2005, pp.25, 1869~1878
- Somanath, P. R., "Akt1 in endothelial cell and angiogenesis", Cell Cycle, 5, pp.512~518 (2006)
- Folkman, J., "Angiogenesis", J. Biol. Chem, 267, pp.10931~10934 (1992)
- Jain, R. K., "Molecular regulation of vessel maturation", Nat. Med, 9, pp.685~693 (2003)
- Shibuya, M., "Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis", Exp. Cell Res, 312, pp.549~560 (2006)
- Gaengel, K., "Endothelial-mural cell signaling in vascular development and angiogenesis", Arterioscler. Thromb. Vasc. Biol, 29, pp.630~638 (2009)
- Hellstrom, M., "Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse", Development, 126, pp.3047~3055 (1999)
- Augustin, H. G., "Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system", Nat. Rev. Mol. Cell Biol, 10, pp.165~177 (2009)
- Felcht, M., "Angiopoietin-2 differentially regulates angiogenesis through TIE2and integrin signaling", J. Clin. Invest, 122, pp.1991~2005 (2012)
- Qin, D., "Early vessel destabilization mediated by Angiopoietin-2 and subsequent vessel maturation via Angiopoietin-1 induce functional neovasculature after ischemia", PLoS One, 8, pp.e61831~ (2013)
- Daly, C., "Angiopoietin-2 functions as an autocrine protective factor in stressed endothelial cells", Proc. Natl Acad. Sci. USA, 103, pp.15491~15496 (2006)
- Hegen, A., "Expression of angiopoietin-2 in endothelial cells is controlled by positive and negative regulatory promoter elements", Arterioscler. Thromb. Vasc. Biol, 24, pp.1803~1809 (2004)
- Stratmann, A., "Cell type-specific expression of angiopoietin-1 and angiopoietin-2 suggests a role in glioblastoma angiogenesis", Am. J. Pathol, 153, pp.1459~1466 (1998)
- Sundberg, C., "Stable expression of angiopoietin-1 and other markers by cultured pericytes : Phenotypic similarities to a subpopulation of cells in maturing vessels during later stages of angiogenesis in vivo", Lab. Invest, 82, pp.387~401 (2002)
- Wakui, S., "Localization of Ang-1, -2, Tie-2, and VEGF expression at endothelial-pericyte interdigitation in rat angiogenesis", Lab. Invest, 86, pp.1172~1184 (2006)
- Kopan, R., "The canonical Notch signaling pathway : Unfolding the activation mechanism", Cell, 137, pp.216~233 (2009)
- Domenga, V., "Notch3 is required for arterial identity and maturation of vascular smooth muscle cells", Genes Dev, 18, pp.2730~2735 (2004)
- Ji, Y., "Jagged1", Notch3 signaling modulates hemangioma-derived pericyte proliferation and maturation, 2016, pp.40, 895~907
- Tao, Y. K., "Notch3 deficiency impairs coronary microvascular maturation and reduces cardiac recovery after myocardial ischemia", Int. J. Cardiol, 236, pp.413~422 (2017)
- Zhao, B., "The Hippo-YAP pathway in organ size control and tumorigenesis : an updated version", Genes Dev, 24, pp.862~874 (2010)
- 김완태, "The history and regulatory mechanism of the Hippo pathway", BMB Reports, 51(3), pp.106~118 (2018), 생화학분자생물학회
- Hao, Y., "Tumor suppressor LATS1 is a negative regulator of oncogene YAP", J. Biol. Chem, 283, pp.5496~5509 (2008)
- Yu, F. X., "The Hippo pathway : Regulators and regulations", Genes Dev, 27, pp.355~371 (2013)
- Liu, C. Y., "The hippo tumor pathway promotes TAZ degradation by phosphorylating a phosphodegron and recruiting the SCF{beta}-TrCP E3 ligase", J. Biol. Chem, 285, pp.37159~37169 (2010)
- Zhao, B., "A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP)", Genes Dev, 24, pp.72~85 (2010)
- Azad, T., "The role of YAP and TAZ in angiogenesis and vascular mimicry", Cells, 8, pp.407~ (2019)
- Fan, R., "Regulation of Hippo pathway by mitogenic growth factors via phosphoinositide 3-kinase and phosphoinositide-dependent kinase-1", Proc. Natl Acad. Sci. USA, 110, pp.2569~2574 (2013)
- Zhao, Y., "PI3K positively regulates YAP and TAZ in mammary tumorigenesis through multiple signaling pathways", Mol. Cancer Res, 16, pp.1046~1058 (2018)
- Wang, Y., "Deletion of yes-associated protein(YAP)specifically in cardiac and vascular smooth muscle cells reveals a crucial role for YAP in mouse cardiovascular development", Circ. Res, 114, pp.957~965 (2014)
- Yun, S. J., "Akt1 isoform modulates phenotypic conversion of vascular smooth muscle cells", Biochim. Biophys. Acta, 1842, pp.2184~2192 (2014)
- Bae, S. S., "Isoform-specific regulation of insulindependent glucose uptake by Akt", protein kinase B, 2003, pp.278, 49530~49536
- Livak, K. J., "Analysis of relative gene expression data using realtime quantitative PCR and the 2(-Delta Delta C(T))Method", Methods, 25, pp.402~408 (2001)
- Ha, J. M., "Vascular leakage caused by loss of Akt1 is associated with impaired mural cell coverage", FEBS Open Bio, 9, pp.801~813 (2019)
- Rogers, M. S., "The mouse cornea micropocket angiogenesis assay", Nat. Protoc, 2, pp.2545~2550 (2007)
- He, L., "Single-cell RNA sequencing of mouse brain and lung vascular and vessel-associated cell types", Sci. Data, 5, pp.180160~ (2018)
- Vanlandewijck, M., "A molecular atlas of cell types and zonation in the brain vasculature", Nature, 554, pp.475~480 (2018)
- Kim, E. K., "Linker region of Akt1", protein kinase Balpha mediates plateletderived growth factor-induced translocation and cell migration, 2008, pp.20, 2030~2037
- 김은경, "Lysophosphatidic acid induces cell migration through the selective activation of Akt1", Experimental and Molecular Medicine, 40(4), pp.445~452 (2008), 생화학분자생물학회
- Kim, E. K., "Selective activation of Akt1 by mammalian target of rapamycin complex 2 regulates cancer cell migration, invasion, and metastasis", Oncogene, 30, pp.2954~2963 (2011)
- Caporali, A., "Contribution of pericyte paracrine regulation of the endothelium to angiogenesis", Pharmacol. Ther, 171, pp.56~64 (2017)
- Suri, C., "Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis", Cell, 87, pp.1171~1180 (1996)
- Thurston, G., "Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1", Science, 286, pp.2511~2514 (1999)
- Maisonpierre, P. C., "Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis", Science, 277, pp.55~60 (1997)
- Liu, H., "Notch3 is critical for proper angiogenesis and mural cell investment", Circ. Res, 107, pp.860~870 (2010)
- Varga, J., "AKT-dependent NOTCH3 activation drives tumor progression in a model of mesenchymal colorectal cancer", J. Exp. Med, 217, pp.e20191515~ (2020)
- Basu, S., "Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis", Mol. Cell, 11, pp.11~23 (2003)
- Hooglugt, A., "Endothelial YAP", TAZ signaling in angiogenesis and tumor vasculature, 2020, pp.10, 612802~
- Choi, H. J., "Yes-associated protein regulates endothelial cell contactmediated expression of angiopoietin-2", Nat. Commun, 6, pp.6943~ (2015)
- Kubota, T., "Imbalanced insulin actions in obesity and type 2 diabetes : Key mouse models of insulin signaling pathway", Cell Metab, 25, pp.797~810 (2017)