Role of serotonin in the hepato-gastroIntestinal tract: an old molecule for new perspectives

Lesurtel, Mickaël; Soll, Christopher; Graf, Rolf; Clavien, Pierre‐Alain

doi:10.1007/s00018-007-7377-3

Cited by 123 publications

(109 citation statements)

References 121 publications

(129 reference statements)

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“…Expression pattern analysis of 5-HT signaling pathway genes in HC indicated that the 5-HT receptors htr2b (1.44-fold), htr1d (1.02-fold), htr1f (2.42-fold), and htr5b (2.08-fold), and their downstream signaling pathway genes mapk12 (1.72-fold), creb1 (1.08-fold), creb3l4 (1.57-fold), and src (1.42-fold) were up-regulated at 72 h after PH ( Figure 4A). Lesurtel et al (2008) showed that mRNA expression of the 5-HT receptors htr2a and htr2b were increased after PH, which is consistent with our results. According to the temporal dynamics of these genes, the 5-HT signaling pathway may promote cell differentiation or apoptosis through the RAS and STAT3 signaling pathways, and thus participate in regulating LR during the termination stage ( Figure 4B).…”

Section: Discussionsupporting

confidence: 93%

Gene expression profiling analysis of 5-hydroxytryptamine signaling pathway in rat regenerating liver and different types of liver cells

Chang¹,

Yang²,

Zhao³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We examined the gene expression profiles of the 5-hydroxytryptamine signaling pathway in the regenerating liver and 8 types of liver cells during rat liver regeneration, and explored expression differences in 5-hydroxytryptamine signaling pathway genes at the level of tissues and cells, as well as the role of the pathway on liver regeneration. Eight types of rat regenerating liver cells were isolated using Percoll density-gradient centrifugation and immunomagnetic bead methods. Rat Genome 230 2.0 Array was used to detect expression changes in 5-hydroxytryptamine signaling pathway genes. The results showed that 26, 47, 8, 21, 16, 19, 22, 27, and 20 effects of 5-hydroxytryptamine signaling pathway genes in 8 types of liver cells showed that 26 genes were expressed significantly; the expression trends of 10 genes were the same in the regenerating liver, while others were different. Based on the gene expression profiles of the 8 types of liver cells, 5-hydroxytryptamine promoted hepatocyte proliferation through the RAS and STAT3 signaling pathways, proliferation and differentiation of sinusoidal endothelial cells through the STAT3 signaling pathway, and proliferation and apoptosis of pit cells through the AKT3 signaling pathway. There were large differences in genes involved in 5-hydroxytryptamine signaling at the tissue and cellular levels; thus, liver regeneration should be studied indepth at the cellular level to reveal the molecular mechanism of liver regeneration.

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Section: Discussionsupporting

confidence: 93%

Gene expression profiling analysis of 5-hydroxytryptamine signaling pathway in rat regenerating liver and different types of liver cells

Chang¹,

Yang²,

Zhao³

et al. 2015

Genet. Mol. Res.

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“…The latter can be conjugated with glycine to yield indole-3-acetylglycine (IAA-Gly) [4]. Within the serotonin pathway, Trp is hydroxylated by tryptophan hydroxylase 2 and then decarboxylated by aromatic L-amino acid decarboxylase to form serotonin [5]. Serotonin serves as the precursor for melatonin and 5-hydroxy-indole-3-acetic acid (HIAA).…”

Section: Introductionmentioning

confidence: 99%

Quantitative profiling of tryptophan metabolites in serum, urine, and cell culture supernatants by liquid chromatography–tandem mass spectrometry

et al. 2011

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A sensitive, selective, and comprehensive method for the quantitative determination of tryptophan and 18 of its key metabolites in serum, urine, and cell culture supernatants was developed. The analytes were separated on a C18 silica column by reversed-phase liquid chromatography and detected by electrospray ionization tandem mass spectrometry in positive ion multiple reaction monitoring (MRM) mode, except for indoxyl sulfate which was measured in negative ion MRM mode in a separate run. The limits of detection and lower limits of quantification were in the range of 0.1-50 and 0.5-100 nM, respectively. Fully 13 C isotope-labeled and deuterated internal standards were used to achieve accurate quantification. The applicability of the method to analyze serum, urine, and cell culture supernatants was demonstrated by recovery experiments and the evaluation of matrix effects. Precision for the analysis of serum, urine, and cell culture supernatants ranged between 1.3% and 16.0%, 1.5% and 13.5%, and 1.0% and 17.4%, respectively. The method was applied to analyze changes in tryptophan metabolism in cell culture supernatants from IFN-γ-treated monocytes and immature or mature dendritic cells.

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“…Serotonin (5-hydroxytryptamine, 5HT) is synthesized from L-tryptophan via a rate-limiting reaction catalyzed by two tryptophan hydroxylases encoded by genes with a distinct pattern of expression (TPH1 in periphery, TPH2 in brain) (9). Outside the CNS, 5HT is synthesized and released into the circulation by enterochromaffin cells and is rapidly taken up and stored by platelets and, to a lesser extent, lymphocytes, monocytes, and macrophages (9).…”

mentioning

confidence: 99%

Serotonin Skews Human Macrophage Polarization through HTR2B and HTR7

Casas-Engel

Domínguez-Soto

Sierra‐Filardi

et al. 2013

The Journal of Immunology

184

126

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Besides its role as a neurotransmitter, serotonin (5-hydroxytryptamine, 5HT) regulates inflammation and tissue repair via a set of receptors (5HT1–7) whose pattern of expression varies among cell lineages. Considering the importance of macrophage polarization plasticity for inflammatory responses and tissue repair, we evaluated whether 5HT modulates human macrophage polarization. 5HT inhibited the LPS-induced release of proinflammatory cytokines without affecting IL-10 production, upregulated the expression of M2 polarization–associated genes (SERPINB2, THBS1, STAB1, COL23A1), and reduced the expression of M1-associated genes (INHBA, CCR2, MMP12, SERPINE1, CD1B, ALDH1A2). Whereas only 5HT7 mediated the inhibitory action of 5HT on the release of proinflammatory cytokines, both 5HT2B and 5HT7 receptors mediated the pro-M2 skewing effect of 5HT. In fact, blockade of both receptors during in vitro monocyte-to-macrophage differentiation preferentially modulated the acquisition of M2 polarization markers. 5HT2B was found to be preferentially expressed by anti-inflammatory M2(M-CSF) macrophages and was detected in vivo in liver Kupffer cells and in tumor-associated macrophages. Therefore, 5HT modulates macrophage polarization and contributes to the maintenance of an anti-inflammatory state via 5HT2B and 5HT7, whose identification as functionally relevant markers for anti-inflammatory/homeostatic human M2 macrophages suggests their potential therapeutic value in inflammatory pathologies.

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Role of serotonin in the hepato-gastroIntestinal tract: an old molecule for new perspectives

Cited by 123 publications

References 121 publications

Gene expression profiling analysis of 5-hydroxytryptamine signaling pathway in rat regenerating liver and different types of liver cells

Gene expression profiling analysis of 5-hydroxytryptamine signaling pathway in rat regenerating liver and different types of liver cells

Quantitative profiling of tryptophan metabolites in serum, urine, and cell culture supernatants by liquid chromatography–tandem mass spectrometry

Serotonin Skews Human Macrophage Polarization through HTR2B and HTR7

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