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. |
|---|---|
| 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. |
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| 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 |
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