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A High-Throughput Screen Identifies DYRK inhibitor ID-8 that Stimulates Human Kidney Tubular Proliferation

ABSTRACT: A High-Throughput Screen Identifies DYRK inhibitor ID-8 that Stimulates Human Kidney Tubular Proliferation

PROVIDER: PRJNA449850 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6987800.fastq.gz	Fastqsanger.gz
	SRR6987791.fastq.gz	Fastqsanger.gz
	SRR6987801.fastq.gz	Fastqsanger.gz
	SRR6987792.fastq.gz	Fastqsanger.gz
	SRR6987802.fastq.gz	Fastqsanger.gz

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A High-Throughput Screen Identifies DYRK inhibitor ID-8 that Stimulates Human Kidney Tubular Proliferation

Project description:Use NGS-transcriptome profiling (RNA-seq) to investigate deregulated genes involved in the proliferative effects of ID-8 and Harmine after hypoxia-induced damage in primary human proximal tubular epithelial cells (HPTECs)

2018-12-19 | GSE113039 | GEO

A High-Throughput Screen Identifies DYRK1A Inhibitor ID-8 that Stimulates Human Kidney Tubular Epithelial Cell Proliferation.

Project description:BackgroundThe death of epithelial cells in the proximal tubules is thought to be the primary cause of AKI, but epithelial cells that survive kidney injury have a remarkable ability to proliferate. Because proximal tubular epithelial cells play a predominant role in kidney regeneration after damage, a potential approach to treat AKI is to discover regenerative therapeutics capable of stimulating proliferation of these cells.MethodsWe conducted a high-throughput phenotypic screen using 1902 biologically active compounds to identify new molecules that promote proliferation of primary human proximal tubular epithelial cells in vitro.ResultsThe primary screen identified 129 compounds that stimulated tubular epithelial cell proliferation. A secondary screen against these compounds over a range of four doses confirmed that eight resulted in a significant increase in cell number and incorporation of the modified thymidine analog EdU (indicating actively proliferating cells), compared with control conditions. These eight compounds also stimulated tubular cell proliferation in vitro after damage induced by hypoxia, cadmium chloride, cyclosporin A, or polymyxin B. ID-8, an inhibitor of dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), was the top candidate identified as having a robust proproliferative effect in two-dimensional culture models as well as a microphysiologic, three-dimensional cell culture system. Target engagement and genetic knockdown studies and RNA sequencing confirmed binding of ID-8 to DYRK1A and upregulation of cyclins and other cell cycle regulators, leading to epithelial cell proliferation.ConclusionsWe have identified a potential first-in-class compound that stimulates human kidney tubular epithelial cell proliferation after acute damage in vitro.

| S-EPMC6287872 | biostudies-literature

ID-JPL934

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ID-JPL934

Project description:ID-JPL934 Metagenome

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ID: 1518171

Project description:ID: 1518171 Raw sequence reads

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Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon

Project description:This SuperSeries is composed of the following subset Series: GSE27847: Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon (part 1) GSE27848: Dietary heme stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon (part 2) Refer to individual Series

2011-10-01 | E-GEOD-27849 | biostudies-arrayexpress

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Project description:Compared with traditional manual suturing, mechanical anastomosis can reduce the error caused by human factors. The electric anastomotic device can improve the automation and accuracy of anastomosis, reduce the requirements for doctors’ operation, and establish a more standardized usage specification, thereby reducing the surgical complication rate and improving the quality of anastomosis. The clinical study of electric tubular anastomotic device adopts a multicenter, randomized, parallel controlled non-inferior study design, and randomly groups according to the 1:1 ratio to evaluate the clinical effectiveness and safety of electric tubular anastomotic device compared with conventional manual device.

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Project description:Profiling project of a panel of tubular adenoma and serrated adenoma patient material collected in the Academic Medical Center (AMC) in Amsterdam, The Netherlands. The aim of the study was to compare the expression profiles of different types of colon cancer precursor lesions (tubular versus serrated adenomas) and determine their correspondence with a set of colon cancer patient-derived profiles that have distinct clinical outcomes. 6 serrated adenomas and 7 tubular adenomas are profiled in this study.

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Expression data from proximal tubular cells of proximal tubular cell-specific KAT5 knockout mice

Project description:Isolated proximal tubular cells from proximal tubular cell-specific KAT5 knockout mice for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain the physiological significance of KAT5 in proximal tubular cells.

2021-11-19 | GSE168535 | GEO

COV-ID: A LAMP sequencing approach for high-throughput co-detection of SARS-CoV-2 and influenza virus in human saliva

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2021-04-15 | GSE172118 | GEO

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