ArticleThe Journal of biological chemistry2011
GATA6 promotes angiogenic function and survival in endothelial cells by suppression of autocrine transforming growth factor beta/activin receptor-like kinase 5 signaling.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Characterization of the mammalian prodefinitive angio-hematopoietic lineage.Science immunology · 2025Article
- Single-Cell Analysis Reveals a Critical Role for Macrophage Epsins in Regulating the Origin of Foam Cells in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- YAP contributes to liver injury through mediating capillarization of liver sinusoidal endothelial cells via GATA6/eNOS signaling.Cellular & molecular biology letters · 2025Article
- SCIG: Machine learning uncovers cell identity genes in single cells by genetic sequence codes.Nucleic acids research · 2025Article
- Single-cell analysis reveals the loss of FABP4-positive proliferating valvular endothelial cells relates to functional mitral regurgitation.BMC medicine · 2024Article
- HYPOXIA induces lncRNA HOTAIR for recruiting RELA in papillary thyroid cancer cells to upregulate miR-181a and promote angiogenesis.Journal of endocrinological investigation · 2024Article
- Site-specific genetic and functional signatures of aortic endothelial cells at aneurysm predilection sites in healthy and AngII ApoEAngiogenesis · 2024Article
- LncRNAs Are Key Regulators of Transcription Factor-Mediated Endothelial Stress Responses.International journal of molecular sciences · 2024Review
- Endothelial Gata6 deletion reduces monocyte recruitment and proinflammatory macrophage formation and attenuates atherosclerosis through Cmpk2-Nlrp3 pathways.Redox biology · 2023Article
- GATA6 regulates anti-angiogenic properties in human cardiac fibroblasts via modulating LYPD1 expression.Regenerative therapy · 2023Article
- Epigenetic landscape reveals MECOM as an endothelial lineage regulator.Nature communications · 2023Article
- GATA6 coordinates cross-talk between BMP10 and oxidative stress axis in pulmonary arterial hypertension.Scientific reports · 2023Article
- Article
- Developmental diversity and unique sensitivity to injury of lung endothelial subtypes during postnatal growth.iScience · 2023Article
- Mst1 silencing alleviates hypertensive myocardial injury associated with the augmentation of microvascular endothelial cell autophagy.International journal of molecular medicine · 2022Article
- Endothelial Cell GATA2 Modulates the Cardiomyocyte Stress Response through the Regulation of Two Long Non-Coding RNAs.Biology · 2022Article
- A novel causative functional mutation in GATA6 gene is responsible for familial dilated cardiomyopathy as supported by in silico functional analysis.Scientific reports · 2022Article
- Establishment and Characterization of a Cell Line (S-RMS1) Derived from an Infantile Spindle Cell Rhabdomyosarcoma withInternational journal of molecular sciences · 2021Article
- The interaction of LOXL2 with GATA6 induces VEGFA expression and angiogenesis in cholangiocarcinoma.International journal of oncology · 2019Article
- Genetic and Functional Variants Analysis of theFrontiers in genetics · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the transcriptional regulation of angiogenesis could lead to the identification of novel therapeutic targets. We showed here that the transcription factor GATA6 is expressed in different human primary endothelial cells as well as in vascular endothelial cells of mice in vivo. Activation of endothelial cells was associated with GATA6 nuclear translocation, chromatin binding, and enhanced GATA6-dependent transcriptional activation. siRNA-mediated down-regulation of GATA6 after growth factor stimulation led to a dramatically reduced capacity of macro- and microvascular endothelial cells to proliferate, migrate, or form capillary-like structures on Matrigel. Adenoviral overexpression of GATA6 in turn enhanced angiogenic function, especially in cardiac endothelial microvascular cells. Furthermore, GATA6 protected endothelial cells from undergoing apoptosis during growth factor deprivation. Mechanistically, down-regulation of GATA6 in endothelial cells led to increased expression of transforming growth factor (TGF) β1 and TGFβ2, whereas enhanced GATA6 expression, accordingly, suppressed Tgfb1 promoter activity. High TGFβ1/β2 expression in GATA6-depleted endothelial cells increased the activation of the activin receptor-like kinase 5 (ALK5) and SMAD2, and suppression of this signaling axis by TGFβ neutralizing antibody or ALK5 inhibition restored angiogenic function and survival in endothelial cells with reduced GATA6 expression. Together, these findings indicate that GATA6 plays a crucial role for endothelial cell function and survival, at least in part, by suppressing autocrine TGFβ expression and ALK5-dependent signaling.
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