ArticleAmerican journal of physiology. Lung cellular and molecular physiology2011
Thrombospondin-1 opens the paracellular pathway in pulmonary microvascular endothelia through EGFR/ErbB2 activation.
Article in American journal of physiology. Lung cellular and molecular physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- ITCH-Mediated Ubiquitination and Degradation of THBS1: A Key Mechanism for Enhancing Mitochondrial Biogenesis and Alleviating Mouse Skeletal Muscle Atrophy.Acta physiologica (Oxford, England) · 2026Article
- Expression of JCAD and EGFR in Perineurial Cell-Cell Junctions of Human Inferior Alveolar Nerve.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2023Article
- Macromolecules Absorbed from Influenza Infection-Based Sera Modulate the Cellular Uptake of Polymeric Nanoparticles.Biomimetics (Basel, Switzerland) · 2022Article
- RNAeLife · 2022Article
- Role of thrombospondin‑1 and thrombospondin‑2 in cardiovascular diseases (Review).International journal of molecular medicine · 2020Review
- Thrombospondin1 (TSP1) replacement prevents cerebral cavernous malformations.The Journal of experimental medicine · 2017Article
- Thrombospondin-1 Gene Deficiency Worsens the Neurological Outcomes of Traumatic Brain Injury in Mice.International journal of medical sciences · 2017Article
- Hantavirus Infection Suppresses Thrombospondin-1 Expression in Cultured Endothelial Cells in a Strain-Specific Manner.Frontiers in microbiology · 2016Article
- Revisiting the matricellular concept.Matrix biology : journal of the International Society for Matrix Biology · 2014Review
- Thrombospondin1 in tissue repair and fibrosis: TGF-β-dependent and independent mechanisms.Matrix biology : journal of the International Society for Matrix Biology · 2012Review
- Thrombospondins as key regulators of synaptogenesis in the central nervous system.Matrix biology : journal of the International Society for Matrix Biology · 2012Review
- Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Thrombospondin-1 (TSP1) is a multidomain protein that contains epidermal growth factor (EGF)-like repeats that indirectly activate the EGF receptor (EGFR) and selected downstream signaling pathways. In these studies, we show that TSP1 opens the paracellular pathway in human lung microvascular endothelial cells (HMVEC-Ls) in a dose-, time-, and protein tyrosine kinase (PTK)-dependent manner. TSP1 increased tyrosine phosphorylation of proteins enriched to intercellular boundaries including the zonula adherens (ZA) proteins, vascular endothelial-cadherin, γ-catenin, and p120 catenin. In HMVEC-Ls, EGFR and ErbB2 are expressed at low levels, and both heterodimerize and tyrosine autophosphorylate in response to TSP1. Prior EGFR-selective PTK inhibition with AG1478 or ErbB2-selective PTK inhibition with AG825 protected against TSP1-induced tyrosine phosphorylation of ZA proteins and barrier disruption. Preincubation of HMVEC-Ls with an EGFR ectodomain-blocking antibody also prevented TSP1-induced opening of the paracellular pathway. Therefore, in HMVEC-Ls, TSP1 increases tyrosine phosphorylation of ZA proteins and opens the paracellular pathway, in part, through EGFR/ErbB2 activation. Surprisingly, recombinant TSP1 EGF-like repeats 1-3 and the high-affinity EGFR ligands, EGF, TGF-α, and amphiregulin, each failed to increase paracellular permeability. However, HMVEC-Ls in which EGFR was overexpressed became responsive to the EGF-like repeats of TSP1 as well as to EGF. These studies indicate that TSP1 disrupts the endothelial barrier through EGFR/ErbB2 activation although additional signals are necessary in cells with low receptor expression.
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