Organic Solute Transporter α-β Protects Ileal Enterocytes From Bile Acid–Induced Injury

Ferrebee, Courtney B.; Li, Jianing; Haywood, Jamie; Pachura, Kimberly; Robinson, Brian; Hinrichs, Benjamin H.; Rao, Anuradha; Dawson, Paul A.

doi:10.1016/j.jcmgh.2018.01.006

Cited by 42 publications

(55 citation statements)

References 95 publications

(152 reference statements)

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“…First, BA accumulation in ileal IECs lacking the basolateral BA transporter, OSTα, leads to villous blunting and IEC proliferation in the ileum that is rescued by ablating ASBTdependent BA import. 118 In addition, circulating subsets of proinflammatory CD4 + T helper (T H ) cells-including IL-17A-secreting Th17 and IFNγ-producing Th1 cells-adapt to high local BA concentrations in the ileum by upregulating the xenobiotic transporter, multidrug resistance protein 1 (MDR1, encoded by ABCB1 in humans, Abcb1a and Abcb1b in mice) (Fig. 2).…”

Section: Farsenoid X Receptormentioning

confidence: 99%

“…120 Notably, BAinduced injury, whether in OSTα-deficient IECs or MDR1-deficient T cells, is associated with oxidative stress and overexpression of inflammatory cytokines, akin to the phenotype of hepatocytes in cholestatic livers. [116][117][118][119] PXR, VDR, and CAR all serve to protect cells from BA-driven injury through the transcriptional activation of drug-and BAdetoxifying enzymes-cytochrome P450 enzymes (i.e., CYPs), BA sulfotransferases (i.e., SULTs), and uridine 5′-diphospho-glucuronosyltransferase (i.e., UGTs)-as well as transporters, such as multidrug resistance-associated protein 3 (MRP3, encoded by ABCC3) (Fig. 2).…”

Section: Farsenoid X Receptormentioning

confidence: 99%

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Emerging roles of bile acids in mucosal immunity and inflammation

2019

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Bile acids are cholesterol-derived surfactants that circulate actively between the liver and ileum and that are classically recognized for emulsifying dietary lipids to facilitate absorption. More recent studies, however, have revealed new functions of bile acids; as pleotropic signaling metabolites that regulate diverse metabolic and inflammatory pathways in multiple cell types and tissues through dynamic interactions with both germline-encoded host receptors and the microbiota. Accordingly, perturbed bile acid circulation and/or metabolism is now implicated in the pathogenesis of cholestatic liver diseases, metabolic syndrome, colon cancer, and inflammatory bowel diseases (IBDs). Here, we discuss the three-dimensional interplay between bile acids, the microbiota, and the mucosal immune system, focusing on the mechanisms that regulate intestinal homeostasis and inflammation. Although the functions of bile acids in mucosal immune regulation are only beginning to be appreciated, targeting bile acids and their cellular receptors has already proven an important area of new drug discovery.

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Section: Farsenoid X Receptormentioning

confidence: 99%

Section: Farsenoid X Receptormentioning

confidence: 99%

Emerging roles of bile acids in mucosal immunity and inflammation

2019

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“…Enterocytes utilize short fatty acids as a source of energy; fatty acid metabolism generates reactive oxygen species (ROS), and ROS are also abundant in the intestinal lumen. Upregulation of the Nfe2l2-ARE pathway may help protect differentiating enterocytes from oxidative damage (Ferrebee et al, 2018). The analysis also identified Isx and Ski (both within M3) as putative novel markers of TA cells within the early enterocyte developmental branch; lack of specific markers has hindered isolation of TA cells and further probing of their plasticity.…”

Section: Tspace Analysis Of Mouse Small Intestine Reveals Rare Enteromentioning

confidence: 99%

Exploration of Cell Development Pathways through High-Dimensional Single Cell Analysis in Trajectory Space

et al. 2020

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High-dimensional single cell profiling coupled with computational modeling is emerging as a powerful tool to elucidate developmental programs directing cell lineages. We introduce tSpace, an algorithm based on the concept of ''trajectory space'', in which cells are defined by their distance along nearest neighbor pathways to every other cell in a population. Graphical mapping of cells in trajectory space allows unsupervised reconstruction and exploration of complex developmental sequences. Applied to flow and mass cytometry data, the method faithfully reconstructs thymic T cell development and reveals development and trafficking regulation of tonsillar B cells. Applied to the single cell transcriptome of mouse intestine and C. elegans, the method recapitulates development from intestinal stem cells to specialized epithelial phenotypes more faithfully than existing algorithms and orders C. elegans cells concordantly to the associated embryonic time. tSpace profiling of complex populations is well suited for hypothesis generation in developing cell systems.

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“…3e, S9c) 25,26 , but also Nfe2l2 and Maf associated with the activation of Nfe2l2/Nrf2-antioxidant response element (ARE) pathway 27 . Enterocytes utilize short fatty acids as a source of energy, and fatty acid metabolism generates reactive oxygen species (ROS), and ROS are also abundant in the intestinal lumen 28 . Upregulation of the Nfe2l2-ARE pathway may help protect differentiating enterocytes from oxidative damage 28 .…”

Section: Figure 1 Tspace Orders Thymic T Cells In Correct Developmenmentioning

confidence: 99%

“…Enterocytes utilize short fatty acids as a source of energy, and fatty acid metabolism generates reactive oxygen species (ROS), and ROS are also abundant in the intestinal lumen 28 . Upregulation of the Nfe2l2-ARE pathway may help protect differentiating enterocytes from oxidative damage 28 . The analysis also identifies Isx and Ski (both within M3) as putative markers of TA cells selectively within the early enterocyte developmental branch.…”

Section: Figure 1 Tspace Orders Thymic T Cells In Correct Developmenmentioning

confidence: 99%

Exploration of cell development pathways through high dimensional single cell analysis in trajectory space

Đermadi

Bscheider

Bjegovic

et al. 2018

Preprint

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High-dimensional single cell profiling coupled with computational modeling holds the potential to elucidate developmental sequences and define genetic programs directing cell lineages. Here we introduce an approach to the discovery and exploration of developmental pathways based on the concept of "trajectory space", in which cells are defined not by their phenotype but by their distance along nearest neighbor trajectories to every other cell in a population. We implement a tSpace algorithm, and show that multidimensional profiling of cells in trajectory space allows unsupervised reconstruction of complex developmental sequences. tSpace is robust, scalable, and implements a global approach to trajectory analysis that attempts to preserve both local and distant relationships in developmental pathways. Applied to high dimensional flow and mass cytometry data, the method faithfully reconstructs known branching pathways of thymic T cell development, and reveals patterns of tonsillar B cell development and of B cell migration. Applied to single cell transcriptomic data, the method unfolds the complex developmental sequences and genetic programs leading from intestinal stem cells to specialized epithelial phenotypes. Profiling of complex populations in high-dimensional trajectory space should prove useful for hypothesis generation in developing cell systems.

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Organic Solute Transporter α-β Protects Ileal Enterocytes From Bile Acid–Induced Injury

Cited by 42 publications

References 95 publications

Emerging roles of bile acids in mucosal immunity and inflammation

Emerging roles of bile acids in mucosal immunity and inflammation

Exploration of Cell Development Pathways through High-Dimensional Single Cell Analysis in Trajectory Space

Exploration of cell development pathways through high dimensional single cell analysis in trajectory space

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