ArticleCellular signalling2014
Hepatocyte growth factor triggers distinct mechanisms of Asef and Tiam1 activation to induce endothelial barrier enhancement.
Article in Cellular signalling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 18 citations in OpenAlex.
- A mechanistic computational model of HGF-VEGF-mediated endothelial cell proliferation and vascular permeability.iScience · 2025Article
- Targeted Therapy for Inflammatory Diseases with Mesenchymal Stem Cells and Their Derived Exosomes: From Basic to Clinics.International journal of nanomedicine · 2022Review
- Microtubule-dependent mechanism of anti-inflammatory effect of SOCS1 in endothelial dysfunction and lung injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Microtubules as Major Regulators of Endothelial Function: Implication for Lung Injury.Frontiers in physiology · 2021Review
- Signaling by Small GTPases at Cell-Cell Junctions: Protein Interactions Building Control and Networks.Cold Spring Harbor perspectives in biology · 2018Review
- Sphingolipids Signaling in Lamellipodia Formation and Enhancement of Endothelial Barrier Function.Current topics in membranes · 2018Article
- The hepatocyte growth factor-expressing character is required for mesenchymal stem cells to protect the lung injured by lipopolysaccharide in vivo.Stem cell research & therapy · 2016Article
- SOCS3-microtubule interaction via CLIP-170 and CLASP2 is critical for modulation of endothelial inflammation and lung injury.The Journal of biological chemistryArticle
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Previous reports described an important role of hepatocyte growth factor (HGF) in mitigation of pulmonary endothelial barrier dysfunction and cell injury induced by pathologic agonists and mechanical forces. HGF protective effects have been associated with Rac-GTPase signaling pathway activated by Rac-specific guanine nucleotide exchange factor Tiam1 and leading to enhancement of intercellular adherens junctions. This study tested involvement of a novel Rac-specific activator, Asef, in endothelial barrier enhancement by HGF and investigated a mechanism of HGF-induced Asef activation. Si-RNA-based knockdown of Tiam1 and Asef had an additive effect on attenuation of HGF-induced Rac activation and endothelial cell (EC) barrier enhancement. Tiam1 and Asef activation was abolished by pharmacologic inhibitors of HGF receptor and PI3-kinase. In contrast to Tiam1, Asef interacted with APC and associated with microtubule fraction upon HGF stimulation. EC treatment by low dose nocodazole to inhibit peripheral microtubule dynamics partially attenuated HGF-induced Asef peripheral translocation, but had negligible effect on Tiam1 translocation. These effects were associated with attenuation of HGF-induced barrier enhancement in EC pretreated with low ND dose and activation of Rac and its cytoskeletal effectors PAK1 and cortactin. These data demonstrate, that in addition to microtubule-independent Tiam1 activation, HGF engages additional microtubule- and APC-dependent pathway of Asef activation. These mechanisms may complement each other to provide the fine tuning of Rac signaling and endothelial barrier enhancement in response to various agonists.
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