دورية أكاديمية
Zebrafish Tie-2 shares a redundant role with Tie-1 in heart development and regulates vessel integrity.
العنوان: | Zebrafish Tie-2 shares a redundant role with Tie-1 in heart development and regulates vessel integrity. |
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المؤلفون: | Gjini E; Hubrecht Institute-KNAW and University Medical Centre, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands., Hekking LH, Küchler A, Saharinen P, Wienholds E, Post JA, Alitalo K, Schulte-Merker S |
المصدر: | Disease models & mechanisms [Dis Model Mech] 2011 Jan; Vol. 4 (1), pp. 57-66. Date of Electronic Publication: 2010 Nov 02. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Company of Biologists Ltd Country of Publication: England NLM ID: 101483332 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1754-8411 (Electronic) Linking ISSN: 17548403 NLM ISO Abbreviation: Dis Model Mech Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Cambridge : Company of Biologists Ltd., c2008- |
مواضيع طبية MeSH: | Organogenesis*/drug effects, Blood Vessels/*pathology , Heart/*embryology , Zebrafish/*embryology , Zebrafish Proteins/*metabolism, Animals ; Antigens, CD/metabolism ; Atorvastatin ; Base Sequence ; Blood Vessels/drug effects ; Blood Vessels/embryology ; Blood Vessels/ultrastructure ; Cadherins/metabolism ; Codon, Terminator/genetics ; Embryo, Nonmammalian/drug effects ; Embryo, Nonmammalian/pathology ; Endocardium/drug effects ; Endocardium/pathology ; Gene Knockdown Techniques ; Head/pathology ; Heart/drug effects ; Hemorrhage/pathology ; Heptanoic Acids/pharmacology ; Lymphatic Vessels/drug effects ; Lymphatic Vessels/embryology ; Molecular Sequence Data ; Mutation/genetics ; Myocardium/pathology ; Protein Structure, Tertiary ; Pyrroles/pharmacology ; Receptor, TIE-1/metabolism ; Receptor, TIE-2/chemistry ; Receptor, TIE-2/genetics ; Receptor, TIE-2/metabolism ; Zebrafish Proteins/chemistry ; Zebrafish Proteins/genetics |
مستخلص: | Tie-2 is a member of the receptor tyrosine kinase family and is required for vascular remodeling and maintenance of mammalian vessel integrity. A number of mutations in the human TIE2 gene have been identified in patients suffering from cutaneomucosal venous malformations and ventricular septal defects. How exactly Tie-2 signaling pathways play different roles in both vascular development and vascular stability is unknown. We have generated a zebrafish line carrying a stop mutation in the kinase domain of the Tie-2 receptor. Mutant embryos lack Tie-2 protein, but do not display any defect in heart and vessel development. Simultaneous loss of Tie-1 and Tie-2, however, leads to a cardiac phenotype. Our study shows that Tie-1 and Tie-2 are not required for early heart development, yet they have redundant roles for the maintenance of endocardial-myocardial connection in later stages. Tie-2 and its ligand Angiopoietin-1 have also been reported to play an important role in vessel stability. We used atorvastatin and simvastatin, drugs that cause bleeding in wild-type zebrafish larvae, to challenge vessel stability in tie-2 mutants. Interestingly, recent clinical studies have reported hemorrhagic stroke as a side effect of atorvastatin treatment. Exposure of embryos to statins revealed that tie-2 mutants are significantly protected from statin-induced bleeding. Furthermore, tie-2 mutants became less resistant to bleeding after VE-cadherin knockdown. Taken together, these data show that atorvastatin affects vessel stability through Tie-2, and that VE-cadherin and Tie-2 act in concert to allow vessel remodeling while playing a role in vessel stability. Our study introduces an additional vertebrate model to study in vivo the function of Tie-2 in development and disease. |
References: | Neurology. 2008 Jun 10;70(24 Pt 2):2364-70. (PMID: 18077795) Nat Immunol. 2003 Dec;4(12):1238-46. (PMID: 14608381) Microvasc Res. 1998 Jul;56(1):1-21. (PMID: 9683559) Nat Med. 2006 Feb;12(2):235-9. (PMID: 16462802) Nature. 1995 Jul 6;376(6535):70-4. (PMID: 7596437) Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H107-18. (PMID: 16126815) Nat Cell Biol. 2008 May;10(5):527-37. (PMID: 18425119) Microvasc Res. 2009 Mar;77(2):187-91. (PMID: 18848573) Nat Genet. 2007 Mar;39(3):397-402. (PMID: 17259985) Science. 1999 Dec 24;286(5449):2511-4. (PMID: 10617467) Dev Cell. 2008 Jan;14(1):25-36. (PMID: 18194650) Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9355-8. (PMID: 8415706) Cardiovasc Res. 2001 Feb 16;49(3):659-70. (PMID: 11166279) Dev Dyn. 1995 May;203(1):80-92. (PMID: 7647376) J Cell Biol. 2005 Apr 25;169(2):239-43. (PMID: 15851516) Hum Mol Genet. 2008 Aug 15;17(16):2424-32. (PMID: 18469344) Eur J Hum Genet. 2010 Apr;18(4):414-20. (PMID: 19888299) Dev Biol. 2007 Jul 1;307(1):29-42. (PMID: 17531218) Oncogene. 1995 Nov 16;11(10):2097-103. (PMID: 7478529) Science. 1997 Jul 4;277(5322):55-60. (PMID: 9204896) Dev Dyn. 2008 Mar;237(3):580-91. (PMID: 18224713) Cell. 1996 Dec 27;87(7):1171-80. (PMID: 8980224) Nat Med. 2000 Apr;6(4):460-3. (PMID: 10742156) Development. 1999 Oct;126(20):4569-80. (PMID: 10498691) Development. 2005 Dec;132(23):5199-209. (PMID: 16251212) Science. 2002 Jul 5;297(5578):99-102. (PMID: 12098699) Stroke. 2008 Feb;39(2):497-502. (PMID: 18174491) Genes Dev. 1994 Aug 15;8(16):1897-909. (PMID: 7958865) Dev Dyn. 1998 May;212(1):133-40. (PMID: 9603430) Dev Dyn. 2004 Sep;231(1):33-42. (PMID: 15305285) Circ Res. 2000 Sep 29;87(7):603-7. (PMID: 11009566) Science. 1998 Oct 16;282(5388):468-71. (PMID: 9774272) Cell. 1996 Dec 27;87(7):1181-90. (PMID: 8980225) Biochem Biophys Res Commun. 1993 Aug 31;195(1):301-9. (PMID: 8395828) Cancer Res. 2007 Apr 1;67(7):2927-31. (PMID: 17409396) Methods Mol Med. 2005;105:171-98. (PMID: 15492396) Obstet Gynecol Surv. 2000 Aug;55(8):511-9. (PMID: 10945194) Nature. 2000 Sep 14;407(6801):242-8. (PMID: 11001067) Dev Cell. 2002 Sep;3(3):411-23. (PMID: 12361603) J Biol Chem. 2007 Aug 17;282(33):23910-8. (PMID: 17562701) Circulation. 2009 Jun 23;119(24):3062-9. (PMID: 19506109) Cell. 1999 Jul 23;98(2):147-57. (PMID: 10428027) Blood. 2004 Jun 1;103(11):4150-6. (PMID: 14976056) Development. 2010 Aug;137(16):2653-7. (PMID: 20610484) EMBO J. 1995 Dec 1;14(23):5884-91. (PMID: 8846781) Blood. 1997 Jun 15;89(12):4317-26. (PMID: 9192754) Blood. 2008 Apr 1;111(7):3489-97. (PMID: 18199826) Dev Cell. 2002 Jul;3(1):127-36. (PMID: 12110173) Biochem Biophys Res Commun. 2009 Apr 17;381(4):592-6. (PMID: 19245790) Exp Mol Med. 2009 Mar 31;41(3):133-9. (PMID: 19293632) |
المشرفين على المادة: | 0 (Antigens, CD) 0 (Cadherins) 0 (Codon, Terminator) 0 (Heptanoic Acids) 0 (Pyrroles) 0 (Zebrafish Proteins) 0 (cadherin 5) A0JWA85V8F (Atorvastatin) EC 2.7.10.1 (Receptor, TIE-1) EC 2.7.10.1 (Receptor, TIE-2) EC 2.7.10.1 (tek protein, zebrafish) EC 2.7.10.1 (tie1 protein, zebrafish) |
تواريخ الأحداث: | Date Created: 20101104 Date Completed: 20110406 Latest Revision: 20211020 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC3014345 |
DOI: | 10.1242/dmm.005033 |
PMID: | 21045210 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1754-8411 |
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DOI: | 10.1242/dmm.005033 |