Epithelial Transport
Ontology highlight
ABSTRACT:
SUBMITTER: 
David Nickerson
PROVIDER: 527 | Physiome Model Repository |
REPOSITORIES: PMR
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Project description:The polyamine transport operon in Streptococcus pneumoniae TIGR4 is necessary for survival in murine models of pneumococcal pneumonia. To date, there is no description of polyamine transport dependent pneumococcal gene expression. In this study, we compared gene expression between the wild-type and transport deficient (potABCD) TIGR4 by RNA-Seq analysis.
2017-08-14 | E-MTAB-5951 | biostudies-arrayexpress
Project description:Accurate annotations of genes and their transcripts is a foundation of genomics, but no annotation technique presently combines throughput and accuracy. As a result, the GENCODE reference collection of long noncoding RNAs remains far from complete: many are fragmentary, while thousands more remain uncatalogued. To accelerate lncRNA annotation, we have developed RNA Capture Long Seq (CLS), combining targeted RNA capture with third generation long-read sequencing. We present an experimental re-annotation of the entire GENCODE intergenic lncRNA populations in matched human and mouse tissues. CLS approximately doubles the complexity of targeted loci, both in terms of validated splice junctions and transcript models. Through its identification of full-length transcript models, CLS allows the first definitive measurement of promoter features, gene structure and protein-coding potential of lncRNAs. Thus CLS removes a longstanding bottleneck of transcriptome annotation, generating manual-quality full-length transcript models at high-throughput scales.
2017-01-20 | GSE93848 | GEO
Project description:Humans can be exposed to per- and polyfluoroalkyl substances (PFASs) via many exposure routes, including diet, which may lead to several adverse health effects. So far, little is known about PFAS transport across the human intestinal barrier. In the current study, we aimed to assess the transport of 5 PFASs (PFOS, PFOA, PFNA, PFHxS and HFPO-DA) in a human induced pluripotent stem cell (hiPSC)-derived intestinal epithelial cell (IEC) model. This model was extensively characterized and compared with the widely applied human colonic adenocarcinoma cell line Caco-2 and a human primary IEC-based model, described to most closely resemble in vivo tissue. The hiPSC-derived IEC layers demonstrated polarized monolayers with tight junctions and a mucus layer. The monolayers consisted of enterocytes, stem cells, goblet cells, enteroendocrine cells, and Paneth cells that are also present in native tissue. Transcriptomics analysis revealed distinct differences in gene expression profiles where the hiPSC-derived IECs showed highest expression of intestinal tissue-specific genes relative to the primary IEC-based model, whereas the Caco-2 cells clustered closer to the primary IEC-based model than the hiPSC-derived IECs. The order of PFAS transport was largely similar between the models and the apparent permeability (Papp) values of PFAS in apical to basolateral direction in the hiPSC-derived IEC model were in the following order: PFHxS>PFOA>HFPO-DA>PFNA>PFOS. In conclusion, the hiPSC-derived IEC model highly resembles human intestinal physiology and is therefore a promising novel in vitro model to study transport of chemicals across the intestinal barrier for risk assessment of chemicals.
2024-06-05 | GSE268603 | GEO
Project description:In cell models, changes in the “accessible” pool of plasma membrane (PM) cholesterol are linked with the regulation of ER sterol synthesis and metabolism by the Aster family of nonvesicular transporters. However, the relevance of such nonvesicular transport mechanisms for lipid homeostasis in vivo has not been defined. Here we reveal two physiological contexts that generate accessible PM cholesterol and engage the Aster pathway in liver: fasting and reverse cholesterol transport (RCT). During fasting, adipose tissue–derived fatty acids activate hepatocyte sphingomyelinase to liberate sequestered PM cholesterol. Aster-dependent cholesterol transport during fasting facilitates cholesteryl ester (CE) formation, cholesterol movement into bile, and VLDL production. During RCT, HDL delivers excess cholesterol to the hepatocyte PM through SR-BI. Loss of hepatic Asters impairs cholesterol movement into feces, raises plasma cholesterol levels, and causes cholesterol accumulation in peripheral tissues. These results reveal fundamental mechanisms by which Aster cholesterol flux contributes to hepatic and systemic lipid homeostasis.
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Project description:Amniotic fluid (AF) volume (AFV) is determined primarily by the rate of intramembranous (IM) transport of AF across the amnion. Intramembranous transport is characterized as vesicular endocytotic and transcytotic processes regulated by fetal urine-derived stimulators and AF inhibitors. Our objectives were to utilize a large-scale multiomics approach to decipher the vesicular transport pathways in the amnion and to identify potential transport regulators in AF and fetal urine. We utilized fetal sheep to experimentally induce alterations in IM transport rate and analyze the expression profiles of transcripts and proteins in amnion, AF and fetal urine. Four experimental groups were studied: control (C), urine drainage with reduced IM transport rate and AFV (UD), urine drainage and fluid replacement with decreased IM transport rate but increased AFV (UDR), and intra-amniotic fluid infusion with augmented IM transport rate and AFV (IA). Amnion and fluid samples were subjected to transcriptomics (RNA-Seq) and proteomics studies followed by bioinformatics analyses using Ingenuity Pathway Analysis software. The analyses revealed 9 functional transport pathways and a panel of differentially expressed transcripts and proteins that are known mediators of vesicular transport and energy metabolism. During UD, expressions of endocytosis and trafficking mediators were reduced as compared to controls. Under UDR, expressions of energy metabolism activators increased while trafficking mediators decreased. During IA, expressions of vesicular uptake and transcellular trafficking regulators were enhanced. Co-expression of the motor protein, cytoplasmic dynein light chain-1, in both AF and fetal urine suggest that this molecule may function as a urine-derived stimulator of IM transport.
2019-03-30 | GSE129077 | GEO
Project description:Spatiotemporal protein expression is mediated by active transport and local translation of mRNAs. Key factors of the transport machinery are RNA-binding proteins (RBPs) that recognise mRNAs as cargo for motor-based transport. However, a global view of transported mRNAs with cognate RBP binding sites is missing. Here, we cast a transcriptome-wide view on endosomal mRNP transport in Ustilago maydis by studying the newly identified endosomal RBP Grp1 and the key transport RBP Rrm4 in a comparative iCLIP approach. This uncovered thousand of cargo mRNAs bound by both RBPs.
2018-12-10 | GSE109557 | GEO
Project description:Transcriptome-wide view of endosomal mRNP transport
| PRJNA431390 | ENA
Project description:Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disease leading to a severe developmental delay. Some MCT8 deficient patients are not as severely affected than others due to residual thyroid hormone (TH) transport. Previously, we hypothesized that these patients’ mutations destabilize the MCT8 protein, which consequently will be sent for degradation. We have already demonstrated that the chemical chaperone sodium phenylbutyrate (NaPB) rescues the function of these mutants by stabilizing their protein expression in an overexpressing cell system. Here we expand our previous work and used human iPSC-derived brain microvascular endothelial-like cells (iBMECs) as a model. We could show that NaPB rescues decreased mutant MCT8 expression and restores transport function. Furthermore, we identified MCT10 as another TH transporter that contributes to T3 uptake. The decrease in mutant protein expression could be explained by the activation of components of the unfolded protein response (UPR) machinery. Increased expression after NaPB treatment is a consequence of UPR attenuation and the stabilization of MCT8 mRNA. In conclusion, we demonstrate that NaPB is suitable to stabilize pathogenic missense mutations and activate transport function in a human-derived cell model opening the possibility of repurposing the FDA-approved drug NaPB for MCT8 deficiency.
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Project description:Drugs and other xenobiotics are not only secreted/reabsorbed by the renal proximal tubule epithelial cells (RPTEC) but may also adversely impact kidney function. In vitro models that can afford prediction of toxic effects and model directional transport are in high demand in both drug and chemical safety; accordingly, active development of new models is underway. The objective of this study was to investigate physiological and transport function of various sources of human RPTECs under static and fluidic conditions. We tested TERT1-immortalized RPTECs, including OAT1-, OCT2- and OAT3-overexpressing variants) and two primary RPETC sources. Cells were cultured on transwell membranes in two conditions – static (24-well transwells) and fluidic (transwells placed into PhysioMimix TC12 organ-on-chip platform with 2 L/s flow). We evaluated barrier formation, transport, and gene expression. We show that primary RPTECs may not be suitable for studies of directional transport on transwell membranes because they form an inferior barrier even though they show generally more relevant expression of key transporters, especially when shear stress is present. Both TERT1 and -OAT1 and -OAT3 overexpressing cells formed robust barrier, but it was unaffected by shear stress. TERT1-OAT1 cells exhibited inhibitable pAH transport; shear stress increased pAH transport function of these cells. However, efficient tenofovir secretion and perfluorooctanoic acid (PFOA) reabsorption by TERT1-OAT1 cells were not modulated by shear stress. With respect to gene expression profiles, we found that both TERT1 and TERT1-OAT1 cells exhibited human kidney-like transcriptomes, but that shear stress did not result in an apparent enhancement of the kidney phenotype. Overall, our data show that addition of flow to in vitro studies of the renal proximal tubule may afford benefits in some aspects of kidney function, but that careful consideration of the impact such studies would have on the cost and throughput of the experiments is needed.
2024-10-23 | GSE246180 | GEO
Project description:Spatiotemporal protein expression is mediated by active transport and local translation of mRNAs. Key factors of the transport machinery are RNA-binding proteins (RBPs) that recognise mRNAs as cargo for motor-based transport. However, a global view of transported mRNAs with cognate RBP binding sites is missing. Here, we cast a transcriptome-wide view on endosomal mRNP transport in Ustilago maydis by studying the newly identified endosomal RBP Grp1 and the key transport RBP Rrm4 in a comparative iCLIP approach. This uncovered thousand of cargo mRNAs bound by both RBPs.
2018-12-10 | GSE109560 | GEO