Matrix Gla protein regulates differentiation of endothelial cells derived from mouse embryonic stem cells

详细信息    查看全文

• 作者：Jiayi Yao ; Pierre J. Guihard ; Ana M. Blazquez-Medela ; Yina Guo ; Ting Liu…
• 关键词：Bone morphogenetic proteins ; Endothelial cells ; Differentiation ; Embryonic stem cells ; Matrix Gla protein
• 刊名：Angiogenesis
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：19
• 期：1
• 页码：1-7
• 全文大小：1,359 KB
• 参考文献：1.Le Bras A, Vijayaraj P, Oettgen P (2010) Molecular mechanisms of endothelial differentiation. Vasc Med 15(4):321–331. doi:10.​1177/​1358863X10371685​ PubMed CrossRef
  2.Chiang PM, Wong PC (2011) Differentiation of an embryonic stem cell to hemogenic endothelium by defined factors: essential role of bone morphogenetic protein 4. Development 138(13):2833–2843. doi:10.​1242/​dev.​061440 PubMed CrossRef PubMedCentral
  3.Bostrom K, Tsao D, Shen S, Wang Y, Demer LL (2001) Matrix GLA protein modulates differentiation induced by bone morphogenetic protein-2 in C3H10T1/2 cells. J Biol Chem 276(17):14044–14052. doi:10.​1074/​jbc.​M008103200 PubMed
  4.Zebboudj AF, Imura M, Bostrom K (2002) Matrix GLA protein, a regulatory protein for bone morphogenetic protein-2. J Biol Chem 277(6):4388–4394. doi:10.​1074/​jbc.​M109683200 PubMed CrossRef
  5.Yao Y, Shahbazian A, Bostrom KI (2008) Proline and gamma-carboxylated glutamate residues in matrix Gla protein are critical for binding of bone morphogenetic protein-4. Circ Res 102(9):1065–1074. doi:10.​1161/​CIRCRESAHA.​107.​166124 PubMed CrossRef
  6.Yao Y, Jumabay M, Wang A, Bostrom KI (2011) Matrix Gla protein deficiency causes arteriovenous malformations in mice. J Clin Investig 121(8):2993–3004. doi:10.​1172/​JCI57567 PubMed CrossRef PubMedCentral
  7.Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G (1997) Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 386(6620):78–81. doi:10.​1038/​386078a0 PubMed CrossRef
  8.Yao Y, Jumabay M, Ly A, Radparvar M, Cubberly MR, Bostrom KI (2013) A role for the endothelium in vascular calcification. Circ Res 113(5):495–504. doi:10.​1161/​CIRCRESAHA.​113.​301792 PubMed CrossRef
  9.Glienke J, Schmitt AO, Pilarsky C, Hinzmann B, Weiss B, Rosenthal A, Thierauch KH (2000) Differential gene expression by endothelial cells in distinct angiogenic states. Eur J Biochem 267(9):2820–2830PubMed CrossRef
  10.Enis DR, Dunmore B, Johnson N, Pober JS, Print CG (2008) Antiapoptotic activities of bcl-2 correlate with vascular maturation and transcriptional modulation of human endothelial cells. Endothelium 15(1):59–71. doi:10.​1080/​1062332080209239​3 PubMed CrossRef
  11.Yao Y, Nowak S, Yochelis A, Garfinkel A, Bostrom KI (2007) Matrix GLA protein, an inhibitory morphogen in pulmonary vascular development. J Biol Chem 282(41):30131–30142. doi:10.​1074/​jbc.​M704297200 PubMed CrossRef
  12.Yao Y, Zebboudj AF, Shao E, Perez M, Bostrom K (2006) Regulation of bone morphogenetic protein-4 by matrix GLA protein in vascular endothelial cells involves activin-like kinase receptor 1. J Biol Chem 281(45):33921–33930. doi:10.​1074/​jbc.​M604239200 PubMed CrossRef
  13.Munroe PB, Olgunturk RO, Fryns JP, Van Maldergem L, Ziereisen F, Yuksel B, Gardiner RM, Chung E (1999) Mutations in the gene encoding the human matrix Gla protein cause Keutel syndrome. Nat Genet 21(1):142–144. doi:10.​1038/​5102 PubMed CrossRef
  14.Meier M, Weng LP, Alexandrakis E, Ruschoff J, Goeckenjan G (2001) Tracheobronchial stenosis in Keutel syndrome. Eur Respir J 17(3):566–569PubMed CrossRef
  15.Yao Y, Yao J, Radparvar M, Blazquez-Medela AM, Guihard PJ, Jumabay M, Bostrom KI (2013) Reducing Jagged 1 and 2 levels prevents cerebral arteriovenous malformations in matrix Gla protein deficiency. Proc Natl Acad Sci USA 110(47):19071–19076. doi:10.​1073/​pnas.​1310905110 PubMed CrossRef PubMedCentral
  16.Yao Y, Jumabay M, Ly A, Radparvar M, Wang AH, Abdmaulen R, Bostrom KI (2012) Crossveinless 2 regulates bone morphogenetic protein 9 in human and mouse vascular endothelium. Blood 119(21):5037–5047. doi:10.​1182/​blood-2011-10-385906 PubMed CrossRef PubMedCentral
  17.Czechanski A, Byers C, Greenstein I, Schrode N, Donahue LR, Hadjantonakis AK, Reinholdt LG (2014) Derivation and characterization of mouse embryonic stem cells from permissive and nonpermissive strains. Nat Protoc 9(3):559–574. doi:10.​1038/​nprot.​2014.​030 PubMed CrossRef PubMedCentral
  18.Israely E, Ginsberg M, Nolan D, Ding BS, James D, Elemento O, Rafii S, Rabbany SY (2014) Akt suppression of TGFbeta signaling contributes to the maintenance of vascular identity in embryonic stem cell-derived endothelial cells. Stem Cells 32(1):177–190. doi:10.​1002/​stem.​1521 PubMed CrossRef
  19.Bostrom K, Zebboudj AF, Yao Y, Lin TS, Torres A (2004) Matrix GLA protein stimulates VEGF expression through increased transforming growth factor-beta1 activity in endothelial cells. J Biol Chem 279(51):52904–52913. doi:10.​1074/​jbc.​M406868200 PubMed CrossRef
  20.Yao Y, Bennett BJ, Wang X, Rosenfeld ME, Giachelli C, Lusis AJ, Bostrom KI (2010) Inhibition of bone morphogenetic proteins protects against atherosclerosis and vascular calcification. Circ Res 107(4):485–494. doi:10.​1161/​CIRCRESAHA.​110.​219071 PubMed CrossRef PubMedCentral
  21.Bostrom KI, Jumabay M, Matveyenko A, Nicholas SB, Yao Y (2011) Activation of vascular bone morphogenetic protein signaling in diabetes mellitus. Circ Res 108(4):446–457. doi:10.​1161/​CIRCRESAHA.​110.​236596 PubMed CrossRef PubMedCentral
  22.Bostrom KI, Guihard P, Blazquez Medela AM, Yao J, Moon JH, Penton A, Yao Y (2015) Matrix Gla protein limits pulmonary arteriovenous malformations in ALK1 deficiency. Eur Respir J 45(3):849–852. doi:10.​1183/​09031936.​00114714 PubMed CrossRef PubMedCentral
  23.Luo G, D’Souza R, Hogue D, Karsenty G (1995) The matrix Gla protein gene is a marker of the chondrogenesis cell lineage during mouse development. J Bone Miner Res 10(2):325–334. doi:10.​1002/​jbmr.​5650100221 PubMed CrossRef
  24.Vicente Lopez MA, Vazquez Garcia MN, Entrena A, Olmedillas Lopez S, Garcia-Arranz M, Garcia-Olmo D, Zapata A (2011) Low doses of bone morphogenetic protein 4 increase the survival of human adipose-derived stem cells maintaining their stemness and multipotency. Stem Cells Dev 20(6):1011–1019. doi:10.​1089/​scd.​2010.​0355 PubMed CrossRef
  25.Boyd NL, Dhara SK, Rekaya R, Godbey EA, Hasneen K, Rao RR, West FD 3rd, Gerwe BA, Stice SL (2007) BMP4 promotes formation of primitive vascular networks in human embryonic stem cell-derived embryoid bodies. Exp Biol Med (Maywood) 232(6):833–843
  26.Medici D, Shore EM, Lounev VY, Kaplan FS, Kalluri R, Olsen BR (2010) Conversion of vascular endothelial cells into multipotent stem-like cells. Nat Med 16(12):1400–1406. doi:10.​1038/​nm.​2252 PubMed CrossRef PubMedCentral
  27.Park C, Kim TM, Malik AB (2013) Transcriptional regulation of EC and vascular development. Circ Res 112(10):1380–1400PubMed CrossRef PubMedCentral
  
• 作者单位：Jiayi Yao (1) (2)
  Pierre J. Guihard (1)
  Ana M. Blazquez-Medela (1)
  Yina Guo (1)
  Ting Liu (1) (3)
  Kristina I. Boström (1) (4)
  Yucheng Yao (1) (5)
  
  1. Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095-1679, USA
  2. Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, 76 Western Yanta Road, Xi’an, 710061, China
  3. Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dong Fang Rd, Shanghai, 200127, China
  4. The Molecular Biology Institute at UCLA, Los Angeles, CA, 90095-1570, USA
  5. Division of Cardiology, David Geffen School of Medicine at UCLA, Box 951679, Los Angeles, CA, 90095-1679, USA
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Cancer Research
  Cell Biology
  Cardiology
  Ophthalmology
  
• 出版者：Springer Netherlands
• ISSN：1573-7209

文摘

Matrix Gla protein (MGP) is an antagonist of bone morphogenetic proteins and expressed in vascular endothelial cells. Lack of MGP causes vascular abnormalities in multiple organs in mice. The objective of this study is to define the role of MGP in early endothelial differentiation. We find that expression of endothelial markers is highly induced in Mgp null organs, which, in wild type, contain high MGP expression. Furthermore, Mgp null embryonic stem cells express higher levels of endothelial markers than wild-type controls and an abnormal temporal pattern of expression. We also find that the Mgp-deficient endothelial cells adopt characteristics of mesenchymal stem cells. We conclude that loss of MGP causes dysregulation of early endothelial differentiation. Keywords Bone morphogenetic proteins Endothelial cells Differentiation Embryonic stem cells Matrix Gla protein