Similar Datasets
Project description:To compare the transcriptional profile in renal tubules conditional deletion of Cpt1a, to floxed littermate controls.
2024-03-01 | GSE246150 | GEO
Project description:The cellular response to low oxygen supply is mediated by hypoxia-inducible factors (HIF). Under hypoxic conditions, HIF is stabilized and target genes are induced. Under normoxia, however, HIF is ubiquitinated through the von Hippel-Lindau protein (VHL), which results in proteasomal degradation. HIF activation leads to induction of genes involved in erythropoiesis, angiogenesis, and cell survival. Furthermore, HIF orchestrates a metabolic shift from oxidative phosphorylation to glycolysis to facilitate ATP production under low oxygen conditions. We used microarrays to detail gene expression changes in kidneys with stable HIF activation in renal tubules, which was achieved by tubule-specific VHL ablation. Three week old Pax8-rtTA;LC-1;Vhl-floxed mice (n=4) and control littermates (n=4) were treated with doxycyline in drinking water for two weeks and put back on normal drinking water for one week. Six weeks old mice were sacrificed and kidneys harvested. Total RNA was extracted and hybridized on Affymetrix microarrays.
2014-01-17 | E-GEOD-54172 | biostudies-arrayexpress
Project description:The plasminogen activator inhibitor-2 (PAI-2; encoded by the SerpinB2 gene) has been described in the context of macrophage activation and in cellular senescence. As both mechanisms are important in kidney disease we tested a possible role of PAI-2 in renal injury and repair. Methods:Aging, ischemia/reperfusion injury and unilateral ureteral obstruction were performed on the mice. Bone marrow was transplantefrom SerpinB2-/- to wild-type littermates and vice versa. Primary tubular cells and macrophages from SerpinB2-/- and wildtype mice were used for functional studies and transcriptional profiling. Results: PAI-2 expression was up-regulated in cultured senescent tubular cells and in kidneys of aged mice. In the lack of PAI-2 in SerpinB2-/- mice was associated with enhanced renal fibrosis and an inflammatory phenotype during aging and in kidney injury models. While acute injury was associated with fewer monocytes/macrophages in SerpinB2-/- kidneys the subsequent resolution of inflammation seen in wildtype kidneys was lacking in knockout mice. Conclusion: PAI-2 regulates renal aging, tubular damage, and resolution of inflammation. PAI-2 is crucial for kidney repair in mice .
2019-10-22 | GSE139156 | GEO
Project description:In this study mice were engineered to specifically delete Twist1 or Snail expression in proximal tubular epithelial cells of the kidney (ggt-cre+;Twist flox/flox and ggt-cre+;Snail flox/flox ). These mice and control mice (ggtcre-;Twist flox/flox: these express Twist1, and ggtcre-;Snail flox/flox:these express Snail) were subjected to unilaterial ureteric obstruction. This experiment allows for the collection and analysis of expression in contralateral healthy (HK) kidney adn obstructed disease (DK) kidney. Total RNA was isolated from the contralateral healthy (HK) and obstructed disease (DK) kidneys of 3 mice with ggt-cre-;Twist flox/flox genotype (Wildtype like) and 4 mice with ggt-cre+;Twist flox/flox genotype (loss of Twist1 in proximal tubular epithelial cells), 3 mice with ggt-cre-;Snail flox/flox genotype (Wildtype like) and 3 mice with ggt-cre+;Snail flox/flox genotype (loss of Snail in proximal tubular epithelial cells). Total RNA was also isolated from kidneys of completely healthy mice: 3 mice ggt-cre-;WT, 3 mice ggt-cre+;WT, 3 mice ggt-cre+;Twist flox/flox and 3 ggt-cre+;Snail flox/flox
2015-08-03 | E-GEOD-60685 | biostudies-arrayexpress
Project description:Transcriptome comparison of tubular tissues from kidneys with focal segmental glomerulosclerosis (FSGS) and tubular tissues from the unaffected portion of tumor nephrectomies. High-density Affymetrix Human Transcriptome Arrays (HTA) 2.0 were used for the gene expression analysis.
2018-10-15 | GSE121211 | GEO
Project description:The Hippo/YAP pathway plays a critical role in early embryonic kidney development, but its functions in the adult kidney are less well understood. Our previous work has demonstrated that tubular YAP activation induced by double knockout of the upstream Hippo kinases Mst1 and Mst2 (Mst1/2 dKO) promotes tubular injury and renal inflammation under basal conditions. However, the importance of tubular YAP activation remains to be established in injured kidneys in which many other injurious pathways are simultaneously activated. Several secreted factors were found to be increased by YAP in tubular cells, but how the transcriptional network is altered by YAP is largely unknown. Here, we show that tubular YAP was already activated at 6 h after unilateral ureteral obstruction (UUO). Tubular YAP deficiency greatly attenuated tubular cell over-proliferation, tubular injury and renal inflammation induced by UUO or cisplatin. RNA-Seq, ChIP and luciferase assay revealed that YAP promoted the transcription of the transcription factor KLF5 whereas no interaction between YAP and KLF5 was observed. Consistently, the elevated expression of KLF5 and its target genes in Mst1/2 dKO or UUO kidneys was blocked by ablation of Yap in tubular cells. Inhibition of KLF5 prevented tubular cell over-proliferation, tubular injury and renal inflammation in Mst1/2 dKO kidneys. Therefore, our results demonstrate that tubular YAP is a key player in kidney injury. YAP and KLF5 form a transcriptional cascade, in which tubular YAP activation induced by kidney injury promotes KLF5 transcription. Activation of this cascade induces tubular cell over-proliferation, tubular injury and renal inflammation
2024-05-01 | GSE235443 | GEO
Project description:Increased export of transglutaminase-2 (TG2) by tubular epithelial cells (TECs) into the surrounding interstitium modifies the extracellular homeostatic balance leading to fibrotic membrane expansion. Although silencing of extracellular TG2 ameliorates progressive kidney scarring in animal models of chronic kidney disease, the pathway through which TG2 is secreted from TECs and contributes to disease progression has not been elucidated. In this study, we developed a global proteomic approach to identify binding partners of TG2 responsible for TG2 externalization in kidneys subjected to unilateral ureteric obstruction, using TG2-knockout kidneys as negative controls. We report a robust and unbiased analysis of the membrane interactome of TG2 in fibrotic kidneys relative to the entire proteome post-UUO detected by SWATH-mass spectrometry.
2018-02-07 | PXD008173 | Pride
Project description:Kidney is a vital organ responsible for homeostasis in the body. To retard kidney aging is of great importance for maintaining body health. Whereas the therapeutic strategies targeting against kidney aging are not elucidated. Recent studies show mitochondrial dysfunction is critical for renal tubular cell senescence and kidney aging, however, the underlying mechanisms of mitochondrial dysfunction in kidney aging have not been demonstrated. Herein, we found calcium overload, and the mitochondrial calcium uniporter (MCU) was induced in renal tubular cells and aged kidney. To activate MCU not only triggered mitochondrial calcium overload, but also induced reactive oxygen species (ROS) production and cellular senescence and age-related kidney fibrosis. Inversely, to block MCU or chelate calcium diminished ROS generation, restored mitochondrial homeostasis, and retarded cell senescence and protected against kidney aging. These results demonstrate MCU plays a key role in promote renal tubular cell senescence, which provides a new insight on the therapeutic strategy for fighting against kidney aging.
2024-10-02 | GSE262514 | GEO
Project description:We performed single-cell transcriptomics analyses (10x Chromium 3' v3.1) using dissociated total kidney cells to identify the difference in gene expression patterns and signaling pathways between male and female mouse kidneys after selective induction of ferroptotic stress in renal tubular epithelial cells.
2022-10-27 | GSE197528 | GEO
Project description:The mechanistic target of rapamycin mTORC1 is a key regulator of cell metabolism and autophagy. Despite widespread clinical use of mTOR inhibitors, the role of mTORC1 in renal tubular function and kidney homeostasis remains elusive. By utilizing constitutive and inducible deletion of conditional Raptor alleles in renal tubular epithelial cells, we discovered that mTORC1 deficiency caused a marked concentrating defect, loss of tubular cells and slowly progressive renal fibrosis. Transcriptional profiling revealed that mTORC1 maintains renal tubular homeostasis by controlling mitochondrial metabolism and biogenesis as well as transcellular transport processes involved in counter-current multiplication and urine concentration. Although mTORC2 partially compensated the loss of mTORC1, exposure to ischemia and reperfusion injury exaggerated the tubular damage in mTORC1-deficient mice, and caused pronounced apoptosis, diminished proliferation rates and delayed recovery. These findings identify mTORC1 as an essential regulator of tubular energy metabolism and as a crucial component of ischemic stress responses. Pharmacological inhibition of mTORC1 likely affects tubular homeostasis, and may be particularly deleterious if the kidney is exposed to acute injury. Furthermore, the combined inhibition of mTORC1 and mTORC2 may increase the susceptibility to renal damage. Raptor fl/fl*KspCre and Raptor fl/fl animals were sacrificed at P14 before the development of an overt functional phenotype. Kidneys were split in half and immediately snap frozen in liquid nitrogen.
2014-06-09 | E-GEOD-54417 | biostudies-arrayexpress