دورية أكاديمية

Endothelial loss of Fzd5 stimulates PKC/Ets1-mediated transcription of Angpt2 and Flt1.

التفاصيل البيبلوغرافية
العنوان: Endothelial loss of Fzd5 stimulates PKC/Ets1-mediated transcription of Angpt2 and Flt1.
المؤلفون: Brandt MM; Experimental Cardiology, Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands., van Dijk CGM; Department of Nephrology and Hypertension, Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands., Chrifi I; Experimental Cardiology, Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands., Kool HM; Department of Pediatric Surgery of the Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands., Bürgisser PE; Department of Pediatric Surgery of the Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands., Louzao-Martinez L; Department of Nephrology and Hypertension, Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands., Pei J; Department of Nephrology and Hypertension, Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands., Rottier RJ; Department of Pediatric Surgery of the Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands., Verhaar MC; Department of Nephrology and Hypertension, Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands., Duncker DJ; Experimental Cardiology, Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands., Cheng C; Experimental Cardiology, Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands. K.L.Cheng-2@umcutrecht.nl.; Department of Nephrology and Hypertension, Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands. K.L.Cheng-2@umcutrecht.nl.
المصدر: Angiogenesis [Angiogenesis] 2018 Nov; Vol. 21 (4), pp. 805-821. Date of Electronic Publication: 2018 May 29.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Springer Country of Publication: Germany NLM ID: 9814575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7209 (Electronic) Linking ISSN: 09696970 NLM ISO Abbreviation: Angiogenesis Subsets: MEDLINE
أسماء مطبوعة: Publication: Dec. 2004- : Berlin : Springer
Original Publication: London ; Philadelphia : Rapid Science Publishers,
مواضيع طبية MeSH: Neovascularization, Physiologic* , Transcription, Genetic* , Wnt Signaling Pathway*, Angiopoietin-1/*metabolism , Frizzled Receptors/*deficiency , Human Umbilical Vein Endothelial Cells/*metabolism , Protein Kinase C/*metabolism , Proto-Oncogene Protein c-ets-1/*metabolism , Vascular Endothelial Growth Factor Receptor-1/*metabolism, Angiopoietin-1/genetics ; Cell Proliferation ; Gene Knockdown Techniques ; Human Umbilical Vein Endothelial Cells/cytology ; Humans ; Protein Kinase C/genetics ; Proto-Oncogene Protein c-ets-1/genetics ; Vascular Endothelial Growth Factor Receptor-1/genetics
مستخلص: Aims: Formation of a functional vascular system is essential and its formation is a highly regulated process initiated during embryogenesis, which continues to play important roles throughout life in both health and disease. In previous studies, Fzd5 was shown to be critically involved in this process and here we investigated the molecular mechanism by which endothelial loss of this receptor attenuates angiogenesis.
Methods and Results: Using short interference RNA-mediated loss-of-function assays, the function and mechanism of signaling via Fzd5 was studied in human endothelial cells (ECs). Our findings indicate that Fzd5 signaling promotes neovessel formation in vitro in a collagen matrix-based 3D co-culture of primary vascular cells. Silencing of Fzd5 reduced EC proliferation, as a result of G 0 /G 1 cell cycle arrest, and decreased cell migration. Furthermore, Fzd5 knockdown resulted in enhanced expression of the factors Angpt2 and Flt1, which are mainly known for their destabilizing effects on the vasculature. In Fzd5-silenced ECs, Angpt2 and Flt1 upregulation was induced by enhanced PKC signaling, without the involvement of canonical Wnt signaling, non-canonical Wnt/Ca 2+ -mediated activation of NFAT, and non-canonical Wnt/PCP-mediated activation of JNK. We demonstrated that PKC-induced transcription of Angpt2 and Flt1 involved the transcription factor Ets1.
Conclusions: The current study demonstrates a pro-angiogenic role of Fzd5, which was shown to be involved in endothelial tubule formation, cell cycle progression and migration, and partly does so by repression of PKC/Ets1-mediated transcription of Flt1 and Angpt2.
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فهرسة مساهمة: Keywords: Angiogenesis; Endothelial cells; Fzd5; Wnt signaling
المشرفين على المادة: 0 (ANGPT1 protein, human)
0 (Angiopoietin-1)
0 (ETS1 protein, human)
0 (FZD5 protein, human)
0 (Frizzled Receptors)
0 (Proto-Oncogene Protein c-ets-1)
EC 2.7.10.1 (FLT1 protein, human)
EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
EC 2.7.11.13 (Protein Kinase C)
تواريخ الأحداث: Date Created: 20180531 Date Completed: 20191024 Latest Revision: 20191024
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6208898
DOI: 10.1007/s10456-018-9625-6
PMID: 29845518
قاعدة البيانات: MEDLINE
الوصف
تدمد:1573-7209
DOI:10.1007/s10456-018-9625-6