ArticleMolecular biology of the cell2009
Mislocalized scaffolding by the Na-H exchanger NHE1 dominantly inhibits fibronectin production and TGF-beta activation.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Identifying a Role for the Sodium Hydrogen Exchanger Isoform 1 in Idiopathic Pulmonary Fibrosis: A Potential Strategy to Modulate Profibrotic Pathways.Biomedicines · 2025Article
- Acid-base transporters in the context of tumor heterogeneity.Pflugers Archiv : European journal of physiology · 2024Review
- Ion channels as a therapeutic target for renal fibrosis.Frontiers in physiology · 2022Review
- Inhibition of c-MYC-miRNA 19 Pathway Sensitized CML K562 Cells to Etoposide via NHE1 Upregulation.Oxidative medicine and cellular longevity · 2022Article
- Roles of the NaInternational journal of molecular sciences · 2021Article
- TGFβ Signaling Increases Net Acid Extrusion, Proliferation and Invasion in Panc-1 Pancreatic Cancer Cells: SMAD4 Dependence and Link to Merlin/NF2 Signaling.Frontiers in oncology · 2020Article
- Cancer-associated arginine-to-histidine mutations confer a gain in pH sensing to mutant proteins.Science signaling · 2017Article
- Glioma-mediated microglial activation promotes glioma proliferation and migration: roles of Na+/H+ exchanger isoform 1.Carcinogenesis · 2016Article
- Oxidative Stress-Activated NHE1 Is Involved in High Glucose-Induced Apoptosis in Renal Tubular Epithelial Cells.Yonsei medical journal · 2016Article
- Hypoxia increases the abundance but not the assembly of extracellular fibronectin during epithelial cell transdifferentiation.Journal of cell science · 2015Article
- pH sensing by FAK-His58 regulates focal adhesion remodeling.The Journal of cell biology · 2013Article
- Aberrant dynamin 2-dependent Na(+) /H(+) exchanger-1 trafficking contributes to cardiomyocyte apoptosis.Journal of cellular and molecular medicine · 2013Article
- Decreased tumor progression and invasion by a novel anti-cell motility target for human colorectal carcinoma cells.PloS one · 2013Article
- Cell volume regulation in epithelial physiology and cancer.Frontiers in physiology · 2013Review
- Considering protonation as a posttranslational modification regulating protein structure and function.Annual review of biophysics · 2013Review
- Dysregulated pH: a perfect storm for cancer progression.Nature reviews. Cancer · 2011Review
- A human MAP kinase interactome.Nature methods · 2010Article
- Role of osteopontin in oral epithelial dysplasia, oral submucous fibrosis and oral squamous cell carcinoma.Journal of oral and maxillofacial pathology : JOMFPArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Secretion and assembly of the extracellular matrix protein fibronectin regulates a number of normal cell and tissue functions and is dysregulated in disease states such as fibrosis, diabetes, and cancer. We found that mislocalized scaffolding by the plasma membrane Na-H exchanger NHE1 suppresses fibronectin expression, secretion, and assembly. In fibroblasts, wild-type NHE1 localizes to the distal margin of membrane protrusions or lamellipodia but a mutant NHE1-KRA2 lacking binding sites for PI(4,5)P2 and the ERM proteins ezrin, radixin, and moesin is mislocalized and found uniformly along the plasma membrane. Although NHE1 regulates intracellular pH homeostasis, fibronectin production is not regulated by changes in intracellular pH, nor is it attenuated in NHE1-deficient cells, indicating fibronectin expression is independent of NHE1 activity. However, fibronectin production is nearly absent in cells expressing NHE1-KRA2 because scaffolding by NHE1 is mislocalized. Additionally, secretion of active but not latent TGF-beta is reduced and exogenous TGF-beta restores fibronectin secretion and assembly. Our data indicate that scaffolding by NHE1-KRA2 dominantly suppresses fibronectin synthesis and TGF-beta activation, and they suggest that NHE1-KRA2 can be used for obtaining a mechanistic understanding of how fibronectin production is regulated and speculatively for therapeutic control of dysregulated production in pathological conditions.
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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.