Kidney Metabolism Modeling System (Kidney on a Chip)
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ABSTRACT:
PROVIDER: PRJNA497704 | ENA |
REPOSITORIES: ENA
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Project description:Kidney Metabolism Modeling System (Kidney on a Chip)
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Project description:Microphysiological System Modeling of Ochratoxin A-Associated Nephrotoxicity
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Project description:Ochratoxin A (OTA) is one of the most abundant mycotoxin contaminants in food stuffs and possesses carcinogenic, nephrotoxic, teratogenic and immunotoxic properties. Especially, severe nephrotoxicity is of great concern, as characterized by degeneration of epithelial cells of the proximal tubules and interstitial fibrosis. However, its mechanism of toxicity, hazard identification as well as genetic risk factors contributing to OTA toxicity in humans has been elusive due to the lack of adequate models that fully recapitulate kidney function in vitro. The present study attempts to evaluate dose-response relationships, identify the contribution of active transport proteins that govern renal disposition of OTA, and determine the role of metabolism in bioactivation and detoxification of OTA using a 3D human kidney proximal tubule microphysiological system (kidney MPS). We demonstrated that IC50 values of OTA in kidney MPS culture (0.375 – 1.21 µM) were in good agreement with clinical toxic concentrations of OTA in urine. Surprisingly, no enhancement of kidney injury biomarkers was evident in the effluents of kidney MPS after OTA exposure despite significant toxicity observed by LIVE/DEAD staining, rather these biomarkers were decreased in OTA concentration-dependent manner. Furthermore, the effect of 1-aminobenzotriazole (ABT) and 6-(NBD-4-ylthio-) hexanol (NBDHEX), pan-inhibitor of P450 and GST enzymes, respectively, on the OTA-induced toxicity in kidney MPS was examined, which resulted in significant enhancement of OTA-induced toxicity by NBDHEX (3 µM) treatment whereas ABT (1 mM) treatment decreased OTA-induced toxicity, suggesting the roles of GSTs and P450 enzymes in the detoxification and bioactivation of OTA, respectively. Additionally, OTA transport studies using kidney MPS in the presence and absence of inhibitor of organic anion transporter(s), probenecid (1 mM), revealed the role of organic anionic membrane transporter(s) in the kidney specific disposition of OTA. Our findings provide a better understanding of the mechanism of OTA-induced kidney injury which may support changes in risk assessment, regulatory agency policies on allowable exposure levels and determination of genetic factors in high-risk populations against OTA nephrotoxicity.
2020-10-22 | GSE151776 | GEO
Project description:Mangrove-derived Streptomyces xiamenensis 318, with a relatively compact genome and simpler secondary metabolism, is used as model organism in our investigation. We performed integrated studies of metabolic dynamical modeling, transcriptome level measurements, and metabolic profiling experiments on this strain. To explore the relationship between primary and secondary metabolism, the global gene expression levels of strain 318 from early stationary phase to late stationary phase were compared by RNAseq analysis at 16 hour, 24 hour, 36 hour and 72 hour after batch culture started.
2019-02-10 | E-MTAB-7314 | biostudies-arrayexpress
Project description:We developed novel chemically defined recipe media named NPSR-v2, that was capable of expanding mouse and human nephron progenitor cells (NPC) for long term culture in vitro in 2D (2 Dimension) format. NPSR-v2 and these expanded NPC can be used for versatile application, such as reprograming, whole genome-wide CRISPR screen, kidney-associated disease modeling and library drug screening etc.
2024-03-14 | GSE230707 | GEO
Project description:Enhancer Regulation in Kidney Repair [ChIP-seq]
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Project description:Aging-related diseases and their comorbidities affect the life quality of a constantly growing proportion of our population. Age-associated changes of kidney structure and function are considerable contributors to the dramatically increased incidence of chronic kidney disease world-wide which has been identified to be a prominent cardiovascular risk factor. In order to detect molecular mechanisms involved in kidney aging we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by a three-layered omics strategy. To this end, transcriptomic, proteomic and targeted lipidomic profiles of young and aged mice were generated and integrated. Transcriptome and proteome analyses revealed differential expression of genes involved primarily in lipid metabolism and immune response. Additional lipidomic analyses uncovered significant age-related differences in the total amount of phosphatidylethanolamines, phosphatidylcholines and sphingomyelins as well as in subspecies of phosphatidylserines and ceramides, while total ceramide levels remained unchanged. By integration of these datasets we identified Aldh1a1, a key enzyme in vitamin A metabolism specifically expressed in the medullary ascending limb, as one of the most prominent upregulated proteins in old kidneys. Moreover, ceramidase Asah1 was highly expressed in aged kidneys, consistent with a decrease in ceramide C16. In summary, our data suggest that changes in lipid metabolism are involved in the process of kidney aging and in the development of chronic kidney disease. 14 weeks females (4 replicates); 96 weeks females (5 replicates)
2015-10-30 | E-GEOD-74463 | biostudies-arrayexpress