ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2011
Epidermal growth factor upregulates serotonin transporter in human intestinal epithelial cells via transcriptional mechanisms.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Transport pathways across the blood-brain barrier for waste clearance and drug delivery.Fluids and barriers of the CNS · 2026Review
- Hepatocyte nuclear factor-4α regulates expression of the serotonin transporter in intestinal epithelial cells.American journal of physiology. Cell physiology · 2020Article
- Glucagon‑like peptide‑1 analogue exendin‑4 modulates serotonin transporter expression in intestinal epithelial cells.Molecular medicine reports · 2020Article
- Serotonin transporter untranslated regions influence mRNA abundance and protein expression.Gene reports · 2020Article
- Antidiarrheal Effect of Sechang-Zhixie-San on Acute Diarrhea Mice and Network Pharmacology Deciphering Its Characteristics and Potential Mechanisms.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Enteric neuroplasticity and dysmotility in inflammatory disease: key players and possible therapeutic targets.American journal of physiology. Gastrointestinal and liver physiology · 2019Review
- Genome-wide association scan for QTL and their positional candidate genes associated with internal organ traits in chickens.BMC genomics · 2019Article
- Association of polymorphic variants in serotonin re-uptake transporter gene with Crohn's disease: a retrospective case-control study.Croatian medical journal · 2018Article
- Serotonin is an endogenous regulator of intestinal CYP1A1 via AhR.Scientific reports · 2018Article
- Regulation of the serotonin transporter in the pathogenesis of irritable bowel syndrome.World journal of gastroenterology · 2016Review
- Transcriptional modulation of SLC26A3 (DRA) by sphingosine-1-phosphate.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Lactobacillus acidophilus stimulates intestinal P-glycoprotein expression via a c-Fos/c-Jun-dependent mechanism in intestinal epithelial cells.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Early Adaptation of Small Intestine After Massive Small Bowel Resection in Rats.Iranian journal of pediatrics · 2015Article
- Mechanisms of Intestinal Serotonin Transporter (SERT) Upregulation by TGF-β1 Induced Non-Smad Pathways.PloS one · 2015Article
- Epidermal growth factor upregulates serotonin transporter and its association with visceral hypersensitivity in irritable bowel syndrome.World journal of gastroenterology · 2014Article
- The role of EGFR and ErbB family related proteins in the oligodendrocyte specification in germinal niches of the adult mammalian brain.Frontiers in cellular neuroscience · 2013Review
- Regulation of intestinal serotonin transporter expression via epigenetic mechanisms: role of HDAC2.American journal of physiology. Cell physiology · 2013Article
- Modulation of human serotonin transporter expression by 5-HTTLPR in colon cells.International journal of molecular sciences · 2011Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Serotonin transporter (SERT) regulates extracellular availability of serotonin and is a potential pharmacological target for gastrointestinal disorders. A decrease in SERT has been implicated in intestinal inflammatory and diarrheal disorders. However, little is known regarding regulation of SERT in the intestine. Epidermal growth factor (EGF) is known to influence intestinal electrolyte and nutrient transport processes and has protective effects on intestinal mucosa. Whether EGF regulates SERT in the human intestine is not known. The present studies examined the regulation of SERT by EGF, utilizing Caco-2 cells grown on Transwell inserts as an in vitro model. Treatment with EGF from the basolateral side (10 ng/ml, 24 h) significantly stimulated SERT activity (∼2-fold, P < 0.01) and mRNA levels compared with control. EGF increased the activities of the two alternate promoter constructs for human SERT gene: SERT promoter 1 (hSERTp1, upstream of exon 1a) and SERT promoter 2 (hSERTp2, upstream of exon 2). Inhibition of EGF receptor (EGFR) tyrosine kinase activity by PD168393 (1 nM) blocked the stimulatory effects of EGF on SERT promoters. Progressive deletions of the SERT promoter indicated that the putative EGF-responsive elements are present in the -672/-472 region of the hSERTp1 and regions spanning -1195/-738 and -152/+123 of hSERTp2. EGF markedly increased the binding of Caco-2 nuclear proteins to the potential AP-1 cis-elements present in EGF-responsive regions of hSERTp1 and p2. Overexpression of c-jun but not c-fos specifically transactivated hSERTp2, with no effects on hSERTp1. Our findings define novel mechanisms of transcriptional regulation of SERT by EGF via EGFR at the promoter level that may contribute to the beneficial effects of EGF in gut disorders.
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