ArticleThe Journal of physiology2012
Epidermal growth factor chronically upregulates Ca(2+)-dependent Cl(-) conductance and TMEM16A expression in intestinal epithelial cells.
Article in The Journal of physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Molecular Mechanisms of Electric Signals Generated at Corneal Wounds.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Epithelial Chloride and Bicarbonate Transport in Intestinal Barrier Failure: A Molecular Target-Validation Assessment of CFTR and SLC26A3/DRA in Inflammatory Bowel Disease.International journal of molecular sciences · 2026Review
- Dynamic single-nucleus transcriptomic profiling of kidney development in Bamaxiang pigs and wild boar.Zoological research · 2026Article
- Effects of natural products on functional constipation: analysis of active ingredient and mechanism.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Live Calcium Imaging of Virus-Infected Human Intestinal Organoid Monolayers Using Genetically Encoded Calcium Indicators.Journal of visualized experiments : JoVE · 2024Article
- A review of platelet-rich plasma for enteric fistula management.Frontiers in bioengineering and biotechnology · 2023Review
- Molecular mechanisms of activation and regulation of ANO1-Encoded CaChannels (Austin, Tex.) · 2021Review
- The diverse roles of TMEM16A CaJournal of advanced research · 2021Review
- Epidermal growth factor strongly affects epithelial NaScientific reports · 2021Article
- Magnesium Absorption in Intestinal Cells: Evidence of Cross-Talk between EGF and TRPM6 and Novel Implications for Cetuximab Therapy.Nutrients · 2020Article
- Potentiation of calcium-activated chloride secretion and barrier dysfunction may underlie EGF receptor tyrosine kinase inhibitor-induced diarrhea.Physiological reports · 2020Article
- Dual role of CaCell death & disease · 2020Article
- Calcium-Activated Chloride Channel ANO1/TMEM16A: Regulation of Expression and Signaling.Frontiers in physiology · 2020Review
- Epidermal growth factor upregulates expression of MUC5AC via TMEM16A, in chronic rhinosinusitis with nasal polyps.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2020Article
- The multifaceted role of TMEM16A in cancer.Cell calcium · 2019Review
- Evidence for metabotropic function of epithelial nicotinic cholinergic receptors in rat colon.British journal of pharmacology · 2019Article
- Normal Calcium-Activated Anion Secretion in a Mouse Selectively Lacking TMEM16A in Intestinal Epithelium.Frontiers in physiology · 2019Article
- Control of Ion Transport by Tmem16a Expressed in Murine Intestine.Frontiers in physiology · 2019Article
- Role of Epidermal Growth Factor Receptor (EGFR) and Its Ligands in Kidney Inflammation and Damage.Mediators of inflammation · 2018Review
- Targeting the PI3K/Akt/mTOR signalling pathway in Cystic Fibrosis.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulated epithelial fluid and electrolyte transport is a common feature of many intestinal disorders. However, molecular mechanisms that regulate epithelial transport processes are still poorly understood, thereby limiting development of new therapeutics. Previously, we showed that epidermal growth factor (EGF) chronically enhances intestinal epithelial secretory function. Here, we investigated a potential role for altered expression or activity of apical Cl(−) channels in mediating the effects of EGF. Cl(−) secretion across monolayers of T(84) colonic epithelia was measured as changes in short-circuit current. Protein expression/phosphorylation was measured by RT-PCR and Western blotting. Under conditions that specifically isolate apical Ca(2+)-activated Cl(−) channel (CaCC) currents, EGF pretreatment (100 ng ml(−1) for 15 min) potentiated carbachol (CCh)-induced responses to 173 ± 25% of those in control cells, when measured 24 h later (n = 26; P < 0.01). EGF-induced increases in CaCC currents were abolished by the transmembrane protein 16A (TMEM16A) inhibitor, T16A(inh)-A01 (10 μm). Furthermore, TMEM16A mRNA and protein expression was increased by EGF to 256 ± 38% (n = 7; P < 0.01) and 297 ± 46% (n = 9, P < 0.001) of control levels, respectively. In contrast, EGF did not alter CFTR expression or activity. EGF-induced increases in Cl(−) secretion, CaCC currents and TMEM16A expression were attenuated by a PKCδ inhibitor, rottlerin (20 μm), and a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY290042 (25 μm). Finally, LY290042 inhibited EGF-induced phosphorylation of PKCδ. We conclude that EGF chronically upregulates Ca(2+)-dependent Cl(−) conductances and TMEM16A expression in intestinal epithelia by a mechanism involving sequential activation of PI3K and PKCδ. Therapeutic targeting of EGF receptor-dependent signalling pathways may provide new approaches for treatment of epithelial transport disorders.
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