ArticlePloS one2015
Mechanisms of Intestinal Serotonin Transporter (SERT) Upregulation by TGF-β1 Induced Non-Smad Pathways.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Optogenetic Regulation of Localization and Function of Serotonin Transporter by Modulating Its Interaction with Soluble Guanylate Cyclase.International journal of molecular sciences · 2026Article
- Interaction of serotonin transporter and TGFB1 facilitates histone serotonylation-mediated synaptic plasticity following environmental enrichment in stressed mouse Mus booduga.Epigenetics & chromatin · 2026Article
- Article
- Heteromeric Solute Carriers: Function, Structure, Pathology and Pharmacology.Advances in experimental medicine and biology · 2021Review
- Cronobacter sakazakii Infection in Early Postnatal Rats Impaired Contextual-Associated Learning: a Putative Role of C5a-Mediated NF-κβ and ASK1 Pathways.Journal of molecular neuroscience : MN · 2021Article
- How Serotonin Level Fluctuation Affects the Effectiveness of Treatment in Irritable Bowel Syndrome.Cureus · 2020Review
- Hepatocyte nuclear factor-4α regulates expression of the serotonin transporter in intestinal epithelial cells.American journal of physiology. Cell physiology · 2020Article
- Enteric neuroplasticity and dysmotility in inflammatory disease: key players and possible therapeutic targets.American journal of physiology. Gastrointestinal and liver physiology · 2019Review
- Differential genetic and functional background in inflammatory bowel disease phenotypes of a Greek population: a systems bioinformatics approach.Gut pathogens · 2019Article
- Association of polymorphic variants in serotonin re-uptake transporter gene with Crohn's disease: a retrospective case-control study.Croatian medical journal · 2018Article
- Effect ofWorld journal of gastroenterology · 2018Article
- The injury of serotonin on intestinal epithelium cell renewal of weaned diarrhoea mice.European journal of histochemistry : EJH · 2016Article
- Regulation of the serotonin transporter in the pathogenesis of irritable bowel syndrome.World journal of gastroenterology · 2016Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
TGF-β1 is an important multifunctional cytokine with numerous protective effects on intestinal mucosa. The influence of TGF-β1 on serotonin transporter (SERT) activity, the critical mechanism regulating the extracellular availability of serotonin (5-HT), is not known. Current studies were designed to examine acute effects of TGF-β1 on SERT. Model human intestinal Caco-2 cells grown as monolayer's or as cysts in 3D culture and ex vivo mouse model were utilized. Treatment of Caco-2 cells with TGF-β1 (10 ng/ml, 60 min) stimulated SERT activity (~2 fold, P<0.005). This stimulation of SERT function was dependent upon activation of TGF-β1 receptor (TGFRI) as SB-431542, a specific TGF-βRI inhibitor blocked the SERT stimulation. SERT activation in response to TGF-β1 was attenuated by inhibition of PI3K and occurred via enhanced recruitment of SERT-GFP to apical surface in a PI3K dependent manner. The exocytosis inhibitor brefeldin A (2.5 μM) attenuated the TGF-β1-mediated increase in SERT function. TGF-β1 increased the association of SERT with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) syntaxin 3 (STX3) and promoted exocytosis of SERT. Caco-2 cells grown as cysts in 3D culture recapitulated the effects of TGF-β1 showing increased luminal staining of SERT. Ussing chamber studies revealed increase in 3H-5-HT uptake in mouse ileum treated ex vivo with TGF-β1 (10 ng/ml, 1h). These data demonstrate a novel mechanism rapidly regulating intestinal SERT via PI3K and STX3. Since decreased SERT is implicated in various gastro-intestinal disorders e.g IBD, IBS and diarrhea, understanding mechanisms stimulating SERT function by TGF-β1 offers a novel therapeutic strategy to treat GI disorders.
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