ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2019
Novel noncanonical regulation of soluble VEGF/VEGFR2 signaling by mechanosensitive ion channel TRPV4.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Identification of potential microRNAs and KEGG pathways in denervation muscle atrophy based on meta-analysis.Scientific reports · 2021Pooled it
- Transient receptor potential vanilloid channels in inflammatory bowel diseases: linking inflammation, angiogenesis, and oxidative stress.Inflammopharmacology · 2026Review
- A glucose-enriched lung pre-metastatic niche triggered by matrix stiffness-tuned exosomal miRNAs in hepatocellular carcinoma.Nature communications · 2025Article
- Fallopian tube rheology regulates epithelial cell differentiation and function to enhance cilia formation and coordination.Nature communications · 2024Article
- Management of experimental trabeculectomy filtering blebs via crosslinking of the scleral flap inhibited vascularization.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024Article
- A TRP to Pathological Angiogenesis and Vascular Normalization.Comprehensive Physiology · 2024Review
- Studying Angiogenesis Using Matrigel In Vitro and In Vivo.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Deletion of Endothelial TRPV4 Protects Heart From Pressure Overload-Induced Hypertrophy.Hypertension (Dallas, Tex. : 1979) · 2023Article
- Ion Channels in Gliomas-From Molecular Basis to Treatment.International journal of molecular sciences · 2023Review
- The transient receptor potential channels in rheumatoid arthritis: Need to pay more attention.Frontiers in immunology · 2023Review
- Six Decades of History of Hypertension Research at the University of Toledo: Highlighting Pioneering Contributions in Biochemistry, Genetics, and Host-Microbiota Interactions.Current hypertension reports · 2022Review
- Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy.Journal of hematology & oncology · 2022Review
- TRPV4 Mechanotransduction in Fibrosis.Cells · 2021Review
- Advances in Intracellular Calcium Signaling Reveal Untapped Targets for Cancer Therapy.Biomedicines · 2021Review
- TRPV Protein Family-From Mechanosensing to Cancer Invasion.Biomolecules · 2021Review
- Transient receptor potential vanilloid 4 channel deletion regulates pathological but not developmental retinal angiogenesis.Journal of cellular physiology · 2021Article
- Advances in the study of cancer metastasis and calcium signaling as potential therapeutic targets.Exploration of targeted anti-tumor therapy · 2021Review
- Role of Transient Receptor Potential Vanilloid 4 in Vascular Function.Frontiers in molecular biosciences · 2021Review
- Tumor-Derived Extracellular Vesicles Induce Abnormal AngiogenesisFrontiers in bioengineering and biotechnology · 2021Article
- The transient receptor potential vanilloid 4 (TRPV4) ion channel mediates protease activated receptor 1 (PAR1)-induced vascular hyperpermeability.Laboratory investigation; a journal of technical methods and pathology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
VEGF signaling via VEGF receptor-2 (VEGFR2) is a major regulator of endothelial cell (EC) functions, including angiogenesis. Although most studies of angiogenesis focus on soluble VEGF signaling, mechanical signaling also plays a critical role. Here, we examined the consequence of disruption of mechanical signaling on soluble signaling pathways. Specifically, we observed that small interfering RNA (siRNA) knockdown of a mechanosensitive ion channel, transient receptor potential vanilloid 4 (TRPV4), significantly reduced perinuclear (Golgi) VEGFR2 in human ECs with a concomitant increase in phosphorylation at Y1175 and membrane translocation. TRPV4 knockout (KO) ECs exhibited increased plasma membrane localization of phospho-VEGFR2 compared with normal ECs. The knockdown also increased phospho-VEGFR2 in whole cell lysates and membrane fractions compared with control siRNA-treated cells. siRNA knockdown of TRPV4 enhanced nuclear localization of mechanosensitive transcription factors, yes-associated protein/transcriptional coactivator with PDZ-binding motif via rho kinase, which were shown to increase VEGFR2 trafficking to the plasma membrane. Furthermore, TRPV4 deletion/knockdown enhanced VEGF-mediated migration in vitro and increased expression of VEGFR2 in vivo in the vasculature of TRPV4 KO tumors compared with wild-type tumors. Our results thus show that TRPV4 channels regulate VEGFR2 trafficking and activation to identify novel cross-talk between mechanical (TRPV4) and soluble (VEGF) signaling that controls EC migration and angiogenesis.-Kanugula, A. K., Adapala, R. K., Midha, P., Cappelli, H. C., Meszaros, J. G., Paruchuri, S., Chilian, W. M., Thodeti, C. K., Novel noncanonical regulation of soluble VEGF/VEGFR2 signaling by mechanosensitive ion channel TRPV4.
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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 OpenQuestion graph.