Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Proteomic profiling of drug and nutrient transporter expression by small intestinal region in neonates, pediatrics, and adults

ABSTRACT: Transporters localized to the small intestinal epithelium govern the absorption of many orally administered drugs and nutrients, and thorough characterization of transporter protein abundance is key to accurate prediction of small molecule absorption. Previous studies have reported there are more than 100 solute carrier and ATP-binding cassette superfamilies expressed in the intestine, but only a small subset of these transporter proteins have been quantified with native intestinal tissue. In addition, a majority of published transporter abundance data for the intestine was collected with adult tissue. Here, we report the identification and relative quantification of 87 solute carrier and 18 ATP-binding cassette superfamily transporters by intestinal region in neonatal, pediatric, and adult small intestinal mucosa using data-independent acquisition mass spectrometry. This study identified transporters uniquely expressed by intestinal region in all three age groups and region-associated abundance for 23 SLC/ABC transporters in pediatrics and adults. The protein abundance data reported here provide a valuable resource for the prediction of nutrient and drug absorption and efflux across age and will inform future studies of specific transporters and age-associated differences in transporter abundance.

ORGANISM(S): Homo Sapiens

SUBMITTER: Vicky Sun

PROVIDER: PXD079663 | panorama | Sat Jun 13 00:00:00 BST 2026

REPOSITORIES: PanoramaPublic

ACCESS DATA

Json Xml

Similar Datasets

Quantitative proteome profiling in HEK293 to validate RNAi targets

Project description:The solute carrier (SLC) transporter superfamily are important coordinators of metabolic and cellular homeostasis. Despite their importance for cellular homeostasis, SLCs remain a largely understudied group of proteins regarding their protein interactome. Thus, we conducted a largescale interactome proteomics study to characterize the interactome of roughly 400 of the 450 superfamily members. Within this study, we validated selected SLC-protein interactions by different assays (e.g.: protein stability, transporter activity assays), in combination with RNA interference (RNAi). For a small subset of the targeted interactors, we used full protein profiling by quantitative mass spectrometry to confirm alleviation of the protein abundance upon RNAi. To validate RNAi downregulation of gene expression on protein level, we assessed protein abundance of ZPFL1, LTN1 and NFXL1 after siRNA treatment.

2025-03-03 | PXD055192 | Pride

DNA methylation analysis validates organoids as a viable model for studying human intestinal aging (expression)

Project description:The epithelia of the intestine and colon turn over rapidly and are maintained by adult stem cells at the base of crypts. While the small intestine and colon have distinct, well-characterized physiological functions, it remains unclear if there are fundamental regional differences in stem cell behavior or region-dependent degenerative changes during aging. Mesenchyme-free organoids provide useful tools for investigating intestinal stem cell biology in vitro and have started to be utilized for investigating age-related changes in stem cell function. However, it is unknown whether organoids maintain hallmarks of age in the absence of an aging niche. Here we test whether stem cell enriched organoids preserve the DNA methylation-based aging profiles associated with the tissues and crypts from which they were derived. To address this, we use standard human methylation arrays and the human 'epigenetic clock' as a biomarker of age to analyze in vitro derived three-dimensional stem cell-enriched intestinal organoids. We find that human stem cell-enriched spheroids maintain segmental differences in methylation patterns and that age, as measured by the epigenetic clock, is largely maintained in spheroids. Surprisingly, we find that small intestine spheroids exhibit striking epigenetic age reduction relative to colon spheroids.

2019-12-03 | GSE141255 | GEO

DNA methylation analysis validates organoids as a viable model for studying human intestinal aging (methylation)

2019-12-03 | GSE141254 | GEO

Gestational Age-Dependent Changes in Gene Expression of Metabolic Enzymes and Transporters in Pregnant Mice

Project description:Knowing the gene expression profiles of drug-metabolizing enzymes and transporters throughout gestation is important for understanding the mechanisms of pregnancy-induced changes in drug pharmacokinetics. In this study, we compared gene expression of drug-metabolizing enzymes and transporters in the maternal liver, kidney, small intestine, and placenta of pregnant mice throughout gestation by microarray analysis. Specifically, we investigated cytochrome P450 (Cyp), UDP-glucuronosyltranserase (Ugt), and sulfotransferase (Sult), as well as ATP-binding cassette (Abc) and solute carrier (Slc) transporters. We found that relatively few Ugt and Sult genes were impacted by pregnancy in maternal tissues and placenta. Cyp1a2, most Cyp2 isoforms, Cyp3a11, and Cyp3a13 in the liver were down-regulated, with the greatest changes occurring on gestation days (gd) 15 and 19 compared to non-pregnant controls (gd 0). However, Cyp2d40, Cyp3a16, Cyp3a41a, Cyp3a41b, and Cyp3a44 in the liver were induced throughout pregnancy. Cyp expression in mid-gestation placenta (gd 10 and 15) was generally greater than that in term placenta (gd 19). There were also notable changes in Abc and Slc transporters. Abcc3 in the liver was down-regulated by 60%, and Abcb1a, Abcc4, and Slco4c1 in the kidney were down-regulated by 30-60% on gd 15 and 19 versus gd 0. Abcc5 in the placenta was induced 3-fold on gd 10 versus gd 15 and 19, whereas Slc22a3 expression in the placenta on gd 10 was 90% lower than that on gd 15 and 19. Overall, this study demonstrates important gestational age-dependent expression of drug-metabolizing enzymes and transporter genes, which may have mechanistic relevance to human pregnancy. Ninety pregnant mice at gestational days 0, 7.5, 10, 15, and 19 (n = 5-6 per gestational age) were used for the maternal liver, kidney, small intestine and placenta. The placentas were collected on gestational days 10, 15, and 19.

2013-10-08 | E-GEOD-41438 | biostudies-arrayexpress

Gene Expression Profiling Reveals Novel Candidate Markers of Ovarian Carcinoma Intraperitoneal Metastasis

Project description:Epithelial ovarian cancer (EOC) has the highest mortality among gynecological carcinomas. The lack of specific markers for prognostic determination of EOC progression hinders the search for novel effective therapies. The aim of the present study was (i) to explore differences in expressions of ATP-binding cassette and solute carrier transporter genes, genes associated with drug metabolism and cell cycle regulation between control ovarian tissues, primary epithelial ovarian carcinomas (EOC) and intraperitoneal EOC metastases; (ii) to investigate associations of gene expression level with prognosis of patients with intraperitoneal metastases.

2017-09-01 | GSE102180 | GEO

Region-specific proteome changes of the intestinal epithelium during aging and dietary restriction

Project description:The small intestine is responsible for nutrient absorption and it is one of the most important interfaces between the environment and our body. During aging, changes in the structure of the epithelium lead to food malabsorption and reduced barrier function thus increasing disease risk in aging. The molecular drivers of these alterations remain poorly understood. Here, we compared the proteomes of small intestinal crypts from mice across different anatomical regions and age groups. We found that aging alters epithelial immune responses, metabolic networks and stem cell proliferation, and it is accompanied by a region-dependent skewing in the cellular composition of the intestinal epithelium. Of note, a short period of dietary restriction followed by re-feeding partially restores the epithelium to a youthful state by promoting the differentiation of intestinal stem cells (ISCs) towards the secretory lineage. Using in vitro and in vivo studies, we identify Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthetase 2) – the rate limiting enzyme in the synthesis of ketone bodies – as a modulator of ISCs differentiation, which responds to dietary changes. This study provides an atlas of age-dependent proteome changes in defined regions of the intestinal epithelium and characterizes how young and old mice adapt to drastic changes of diet, such as dietary restriction and re-feeding.

2020-04-29 | PXD014311 | Pride

Intestinal epithelial cell diversity and function in respect to age, anatomical localization, and microbial exposure - the proximal to distal transcriptome

Project description:The small intestinal epithelium is composed of several defined epithelial cell lineages, which in turn exhibit marked transcriptional and functional diversity along the crypt-villus and proximal-to-distal length of the intestinal tract. While epithelial cell type and functional heterogeneity have been characterized in the adult intestinal epithelium, the temporal and spatial changes during the postanatal period, which accompany the transition from placental energy supply to enteral feeding and facilitate the establishment of the enteric microbiota and postnatal immune maturation, have not been systematically investigated. Here, we analyzed the proximal, medial and distal parts of the small intestinal epithelium of 1-, 5-, 10- and 25-day-old SPF mice by bulk RNA-Seq and used differential gene expression and pathway analysis to identify age-specific expression patterns. We identify gene clusters temporally expressed in the neonatal intestine and correlate their expression with the functional changes during postnatal tissue maturation and the neonate to adult transition.

2024-12-23 | GSE283143 | GEO

Intestinal epithelial cell diversity and function in respect to age, anatomical localization, and microbial exposure - the single cell transcriptome

Project description:The small intestinal epithelium is composed of several defined epithelial cell lineages, which in turn exhibit marked transcriptional and functional diversity along the crypt-villus and proximal-to-distal length of the intestinal tract. While epithelial cell type and functional heterogeneity have been characterized in the adult intestinal epithelium, the temporal and spatial changes during the postanatal period, which accompany the transition from placental energy supply to enteral feeding and facilitate the establishment of the enteric microbiota and postnatal immune maturation, have not been systematically investigated. Here, we analyzed the small intestinal epithelium of 1-, 5-, 10- and 25-day-old SPF mice by single cell RNA-Seq and used differential gene expression and pathway analysis to identify age-specific expression patterns. In addition, the influence of enteric infection on the neonatal epithelium was investigated. We identify gene clusters temporally expressed in the neonatal intestine and correlate their expression with the functional changes during postnatal tissue maturation and the neonate to adult transition.

2024-12-23 | GSE284074 | GEO

Loss of Hepatocyte-Nuclear-Factor-1α Impacts on Adult Mouse Intestinal Epithelial Cell Growth and Cell Lineages Differentiation

Project description:Although hepatocyte-nuclear-factor-1α (Hnf1α) is crucial for pancreas and liver functions, it is believed to play a limited functional role for intestinal epithelial functions. The aim of this study was to assess the consequences of abrogating Hnf1α on the maintenance of adult small intestinal epithelial functions. Methodology/Principal Findings An Hnf1α knockout mouse model was used. Assessment of histological abnormalities, crypt epithelial cell proliferation, epithelial barrier, glucose transport and signalling pathways were measured in these animals. Changes in global gene expression were also analyzed. Mice lacking Hnf1α displayed increased crypt proliferation and intestinalomegaly as well as a disturbance of intestinal epithelial cell lineages production during adult life. This phenotype was associated with a decrease of the mucosal barrier function and lumen-to-blood glucose delivery. The mammalian target of rapamycin (mTOR) signalling pathway was found to be overly activated in the small intestine of adult Hnf1α mutant mice. The intestinal epithelium of Hnf1α null mice displayed a reduction of the enteroendocrine cell population. An impact was also observed on proper Paneth cell differentiation with abnormalities in the granule exocytosis pathway. Conclusions/Significance Together, these results unravel a functional role for Hnf1α in regulating adult intestinal growth and sustaining the functions of intestinal epithelial cell lineages. HNF1alpha was knocked out. A total of 3 control and 3 mutant littermate individuals were sacrificed at 4 months of age. The jejunum was harvested and total RNA was isolated from each individual. Each RNA sample was independently used to generate probes to screen Affymetrix chips.

2011-01-01 | E-GEOD-23040 | biostudies-arrayexpress