Thrombin mediates changes in endothelial barrier function and increases endothelial permeability. A feature of thrombin-enhanced endothelial hyperpermeability is contraction of endothelial cells (ECs), accompanied by formation of focal adhesions (FAs). Recently, a G protein-coupled receptor kinase-interacting protein, GIT1, was shown to regulate FA disassembly. We hypothesized that GIT1 modulates thrombin-induced changes in FAs. In human umbilical vein ECs (HUVECs), thrombin recruited GIT1 to FAs, where GIT1 colocalized with FAK and vinculin. Recruitment of GIT1 to FAs was dependent on activation of the small GTPase RhoA, and Rho kinase, as demonstrated by adenoviral transfection of dominant-negative RhoA and treatment with Y-27632. Thrombin stimulated GIT1 tyrosine phosphorylation with a time course similar to FAK phosphorylation in a Rho kinase- and Src-dependent manner. Depletion of GIT1 with antisense GIT1 oligonucleotides had no effect on basal cell morphology, but increased cell rounding and contraction of HUVECs, increased FA formation, and increased FAK tyrosine phosphorylation in response to thrombin, concomitant with increased endothelial hyperpermeability. These data identify GIT1 as a novel mediator in agonist-dependent signaling in ECs, demonstrate that GIT1 is involved in cell shape changes, and suggest a role for GIT1 as a negative feedback regulator that augments recovery of cell contraction.
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http://dx.doi.org/10.1161/01.RES.0000125627.77235.0C | DOI Listing |
Biomed Opt Express
December 2024
Johnson & Johnson MedTech, Van Swietenlaan 5, 9728NX Groningen, The Netherlands.
A new system and methodology are introduced to evaluate photic phenomena induced by different intraocular lens (IOL) technologies using a "see-through" IOL analyzer system in phakic subjects. Nineteen phakic subjects looked through the Groningen IOL Telescope type 1 (GIT1) system under different conditions. Four different IOL designs with different clinical levels of photic phenomena were evaluated by the subjects.
View Article and Find Full Text PDFAJNR Am J Neuroradiol
October 2024
From the Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, UK (U.L.,F.D.), Laboratory of Developmental Biology, CNRS, Sorbonne-University, IPBS, Paris, France (M.C.), Department of Radiology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, United States (M.H.L.), Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy (R.P.), Department of Radiology, Tartu University Hospital, Tartu, Estonia (P.I., D.L., A.T.), Department of Radiology, The University of Tartu, Tartu, Estonia (P.I.), UOC Neuroradiologia, ASST Papa Giovanni XXIII, Bergamo, Italy (G.P.), Department of Radiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK (I.C.), Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy (M.S., A.R.) and Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy (A.R.).
Dis Model Mech
October 2024
Biomechanics and Bioengineering Research Centre Versus Arthritis, Biomedicine Division, School of Biosciences, The Sir Martin Evans Building, Cardiff University, Cardiff CF10 3AX, Wales, UK.
Drug Des Devel Ther
July 2024
Department of Medicinal Chemistry, College of Pharmacy, Third Military Medical University, Chongqing, People's Republic of China.
Background And Objective: GIT1 (G-protein-coupled receptor kinase interacting protein-1) has been found to be highly related with cancer cell invasion and metastasis in many cancer types. β-Pix (p21-activated kinase-interacting exchange factor) is one of the proteins that interact with GIT1. Targeting GIT1/β-Pix complex might be a potential therapeutic strategy for interfering cancer metastasis.
View Article and Find Full Text PDFZhonghua Zhong Liu Za Zhi
July 2024
Departemnt of Otolaryngology, the Fourth Central Hospital of Tianjin, Tianjin 300140, China.
To investigate the influence of circ_BACH2 on the malignant biological behavior of papillary thyroid cancer and its molecular mechanism. Cancer tissues and paracancer tissues of 51 patients with papillary thyroid carcinoma from the Fourth Central Hospital of Tianjin between 2017 and 2019 were collected. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_BACH2, miR-370-3p and G protein coupled receptor kinase interacting factor 1 (GIT1) mRNA in tissues and cells; flow cytometry to detect cell apoptosis and cell cycle; plate clone formation experiment to detect the number of cell clones; cell counting kit 8 (CCK-8) to detect cell proliferation; Transwell array to detect cell migration and invasion; western blot to detect protein expressions; dual luciferase report experiment to detect the targeting relationship between circ_BACH2, miR-370-3p and GIT1; the nude mouse tumor formation experiment to detect the effect of circ_BACH2 on tumors in mice.
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