ArticleBiomedical reports2026
Serotonin inhibits the influx of iron into cells by decreasing the expression of SLC11A2 in Caco-2 cells.
Article in Biomedical reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Iron is an essential trace element for biological functions and its homeostasis is strictly regulated. Intestinal iron absorption primarily occurs in the duodenum, and the iron transporter solute carrier family 11 member 2 (SLC11A2; also known as divalent metal transporter 1) is crucial in this process. Notably, iron absorption is regulated by iron stores in the body and hormones; however, the effects of serotonin on iron transport are poorly understood. The present study aimed to analyze the effects of serotonin on the expression and function of SLC11A2 using human colon carcinoma-derived Caco-2 cells. SLC11A2 mRNA and protein levels were measured using reverse transcription-quantitative PCR and western blotting, respectively. To investigate the effect of serotonin on intracellular iron concentrations, iron levels were measured in cells treated with a soluble iron salt. The results revealed that serotonin decreased SLC11A2 mRNA levels to ~25% and protein levels to ~35% of control values (P<0.01). A soluble iron salt markedly increased the intracellular iron concentration in Caco-2 cells; however, this increase was suppressed by serotonin treatment (P<0.01). To investigate the mechanism of serotonin action, Caco-2 cells were treated with BW723C86, a selective 5-hydroxytryptamine (5-HT) 2B receptor agonist. BW723C86 also decreased SLC11A2 mRNA levels to ~25% and protein levels to ~60% of control values (P<0.01 and P<0.05). Furthermore, BW723C86 suppressed the increase in intracellular iron concentration induced by a soluble iron salt (P<0.01). In addition, the serotonin-induced decrease in SLC11A2 mRNA levels was inhibited by SB204741, a selective antagonist of the 5-HT2B receptor (P<0.05). These findings suggested a novel link between serotonin signaling and iron absorption, which may inform future therapeutic approaches for iron deficiency anemia.
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