Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human renal proximal tube endothelial cells at 24h and 1%oxygen

ABSTRACT: Aim of the study was to characterize the transcriptional response of human primary renal proximal tubule endothelial cells (RPTEC) to low oxygen stress. Experiment Overall Design: Passage 4 renal proximal tubule epithelial cells were exposed to a humidified atmosphere consisting of either 5% CO2 and 95% air (20% O2, normoxia) or 5% CO2, 1% oxygen and 95% nitrogen (hypoxia) for 24 hours. Total RNA was extracted immediately after exposure. Three independent biological replicates were performed, resulting in 6 samples (3 control and 3 low oxygen).

ORGANISM(S): Homo sapiens

SUBMITTER: Peter Staller

PROVIDER: E-GEOD-12792 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Sepsis is a severe and dysregulated inflammatory disease that often precedes the development of acute kidney injury (AKI) with consequent worsening outcome. The main characteristics of sepsis-induced AKI include endothelial cell (EC) dysfunction, infiltration of inflammatory cells, glomerular thrombosis, and renal tubular epithelial cells (RTEC) injury. Numerous studies have demonstrated that mammalian target of rapamycin (mTOR) activation has been implicated in the initiation and progression of renal injury in course of sepsis. However, little is known, about the molecular basis of mTOR role in EC and RTEC dysfunction. Here, we evaluate whether mTOR inhibition by Rapamycin (Rp) as potential strategy to ameliorate renal function and dissected the molecular mechanisms involved. In a mouse model of lipopolysaccharide (LPS)-induced AKI , LPS injection led to a time-dependent increase of serum creatinine and significant morphological changes in renal parenchyma associated with increased collagen deposits and endothelial dysfunction. Interestingly, Rp treatment significantly decreased creatine levels and preserved renal parenchyma, counteracting Endothelial-to mesenchymal transition (EndMT) process and early fibrosis through the inhibition of ERK pathway. Next, we examined the effects of LPS-TLR4 interaction in RTECs. Through a whole-genome DNA methylation analysis in cultured RTEC, we found that LPS induced aberrant methylation, particularly in regions involved in premature aging. The most represented genes were CD39 and WFS1. LPS stimulation of RTEC led to up-regulation of SA-β Gal and cell cycle arrest markers such as p21. In accordance, in endotoxemic mice, we found a decreased expression of CD39 concurrent with Klotho down-regulation. Administration of Rp exerted anti-aging effects in endotoxemic mice, preserving CD39 and Klotho expression. In conclusion, we demonstrated that mTOR inhibition could offer novel strategies to protect endothelial and tubular compartment from accelerated aging and fibrosis thus counteracting the progression to chronic kidney disease.

Dataset Information

Transcription profiling of human renal proximal tube endothelial cells at 24h and 1%oxygen

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets