ArticleProceedings of the National Academy of Sciences of the United States of America2022
WNK1 collaborates with TGF-β in endothelial cell junction turnover and angiogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Histone modification of endothelial-mesenchymal transition in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Pooled it
- Exploring the Role of the SLC12A Cation-Coupled Chloride Cotransporters in the Cardiovascular System.Cells · 2026Review
- With no lysine kinase 1 in hepatic stellate cells promotes mouse and human liver fibrosis through glycolytic triosephosphate isomerase 1.Hepatology (Baltimore, Md.) · 2026Article
- TGF-β and TNF-α Signaling Crosstalk in Human Coronary Artery Cells.International journal of molecular sciences · 2026Article
- Knock-down of the long isoform of the WNK1 kinase mitigates the anti-glomerular basement membrane glomerulonephritis in mice.Scientific reports · 2026Article
- Role of transforming growth factorβ in neurovascular unit during cerebral small vessel disease.Fluids and barriers of the CNS · 2025Review
- LRRC8A in endothelial cells contributes to the aberrant blood-brain barrier integrity in ischaemic stroke.Stroke and vascular neurology · 2025Article
- Identification of sus-PSMB7_0001 as a potential pro-angiogenic circular RNA in neonatal pig hearts.Journal of molecular and cellular cardiology · 2025Article
- Kinase interaction analysis predicts actions of the WNK-OSR1/SPAK pathway.Communications biology · 2025Article
- Activation of WNK1 signaling through Piezo1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Exosomal CircRNAs: A Future Star in Colorectal Cancer.Current cancer drug targets · 2025Review
- Single-cell analysis reveals the loss of FABP4-positive proliferating valvular endothelial cells relates to functional mitral regurgitation.BMC medicine · 2024Article
- Familial Hyperkalemic Hypertension.Comprehensive Physiology · 2024Review
- Network Pharmacology Approaches Used to Identify Therapeutic Molecules for Chronic Venous Disease Based on Potential miRNA Biomarkers.Journal of xenobiotics · 2024Article
- Review
- Purine metabolite inosine induced by transforming growth factor‑β promotes epithelial‑mesenchymal transition in colorectal cancer.Oncology letters · 2024Article
- SMURF1/2 Are Novel Regulators of WNK1 Stability.Kinases and phosphatases · 2024Article
- mFrontiers of medicine · 2024Article
- Microvesicles derived from dermal myofibroblasts modify the integrity of the blood and lymphatic barriers using distinct endocytosis pathways.Journal of extracellular biology · 2024Article
- WNK kinase is a vasoactive chloride sensor in endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Angiogenesis is essential for growth of new blood vessels, remodeling existing vessels, and repair of damaged vessels, and these require reorganization of endothelial cell-cell junctions through a partial endothelial-mesenchymal transition. Homozygous disruption of the gene encoding the protein kinase WNK1 results in lethality in mice near embryonic day (E) 12 due to impaired angiogenesis. This angiogenesis defect can be rescued by endothelial-specific expression of an activated form of the WNK1 substrate kinase OSR1. We show that inhibition of WNK1 kinase activity not only prevents sprouting of endothelial cells from aortic slices but also vessel extension in inhibitor-treated embryos ex vivo. Mutations affecting TGF-β signaling also result in abnormal vascular development beginning by E10 and, ultimately, embryonic lethality. Previously, we demonstrated cross-talk of WNK1 with TGF-β-regulated SMAD signaling, and OSR1 was identified as a component of the TGF-β interactome. However, molecular events jointly regulated by TGF-β and WNK1/OSR1 have not been delineated. Here, we show that inhibition of WNK1 promotes TGF-β-dependent degradation of the tyrosine kinase receptor AXL, which is involved in TGF-β-mediated cell migration and angiogenesis. We also show that interaction between OSR1 and occludin, a protein associated with endothelial tight junctions, is an essential step to enable tight junction turnover. Furthermore, we show that these phenomena are WNK1 dependent, and sensitive to TGF-β. These findings demonstrate intimate connections between WNK1/OSR1 and multiple TGF-β-sensitive molecules controlling angiogenesis and suggest that WNK1 may modulate many TGF-β-regulated functions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.