Cloning and transplantation of adult renal tubular progenitors
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE120049 | GEO | 2022/04/22
REPOSITORIES: GEO
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Project description:Kidney damage involves the progressive and inexorable destruction of tubular and glomerular system. However, it is known that the patients survive AKI often recover renal structure and function. Correspondingly, previous studies demonstrated tubular regeneration in mice after massive kidney injury and linked mouse Sox9+ renal progenitor cells to this process. Here we show that renal progenitor cells can be cloned from renal needle biopsy sample of CKD patients. Progenitor cells can readily assembly into “kidney organoids” expressing proximal/distal tubular cell markers in 3D culture.
2022-04-22 | GSE119426 | GEO
Project description:MicroRNAs (miRNAs) are endogenous small RNAs of 18–23 nucleotides that regulate gene expression. Recently, plasma miRNAs have been investigated as biomarkers for various diseases. In the present study, we assessed whether the miRNA expression profiles of tubular tissues could discriminate proximal tubule injury and diagnose acute kidney injury (AKI) and the renal tubular dysfunction without morphological changes.
2015-03-17 | GSE66134 | GEO
Project description:NF-κB is a key regulator of innate and adaptive immunity and is implicated in the pathogenesis of acute kidney injury (AKI). The cell type-specific functions of NF-κB in the kidney are unknown; however, the pathway serves distinct functions in immune and tissue-parenchymal cells. We analyzed tubular epithelial-specific NF-κB signaling in a mouse model of ischemia-reperfusion injury (IRI)-induced AKI. NF-κB reporter activity and nuclear localization of phosphorylated NF-κB subunit p65 analyses in mice revealed widespread NF-κB activation in renal tubular epithelia and in interstitial cells following IRI that peaked at 2-3 days after injury. To genetically antagonize tubular epithelial NF-κB activity, we generated mice expressing the human NF-κB super-repressor IκBα∆N in renal proximal, distal, and collecting duct epithelial cells. These mice were protected from IRI-induced AKI, as indicated by improved renal function, reduced tubular apoptosis, and attenuated neutrophil and macrophage infiltration. Tubular NF-κB-dependent gene expression profiles revealed temporally distinct functional gene clusters for apoptosis, chemotaxis, and morphogenesis. Primary proximal tubular cells isolated from IκBα∆N-expressing mice exposed to hypoxia-mimetic agent cobalt chloride were protected from apoptosis and expressed reduced levels of chemokines. Our results indicate that postischemic NF-κB activation in renal-tubular epithelia aggravates tubular injury and exacerbates a maladaptive inflammatory response.
2016-09-17 | GSE87024 | GEO
Project description:NF-κB is a key regulator of innate and adaptive immunity and is implicated in the pathogenesis of acute kidney injury (AKI). The cell type-specific functions of NF-κB in the kidney are unknown; however, the pathway serves distinct functions in immune and tissue-parenchymal cells. We analyzed tubular epithelial-specific NF-κB signaling in a mouse model of ischemia-reperfusion injury (IRI)-induced AKI. NF-κB reporter activity and nuclear localization of phosphorylated NF-κB subunit p65 analyses in mice revealed widespread NF-κB activation in renal tubular epithelia and in interstitial cells following IRI that peaked at 2-3 days after injury. To genetically antagonize tubular epithelial NF-κB activity, we generated mice expressing the human NF-κB super-repressor IκBα∆N in renal proximal, distal, and collecting duct epithelial cells. These mice were protected from IRI-induced AKI, as indicated by improved renal function, reduced tubular apoptosis, and attenuated neutrophil and macrophage infiltration. Tubular NF-κB-dependent gene expression profiles revealed temporally distinct functional gene clusters for apoptosis, chemotaxis, and morphogenesis. Primary proximal tubular cells isolated from IκBα∆N-expressing mice exposed to hypoxia-mimetic agent cobalt chloride were protected from apoptosis and expressed reduced levels of chemokines. Our results indicate that postischemic NF-κB activation in renal-tubular epithelia aggravates tubular injury and exacerbates a maladaptive inflammatory response.
2016-09-17 | GSE87023 | GEO
Project description:Acute kidney injury (AKI) have been thought to be reversible condition, however, emerging evidence demonstrated association between AKI and subsequent development of irreversible fibrosis and chronic kidney disease. In the present study, since recovery of AKI depends on renal tubular regeneration, factors expressing in renal tubules in adaptive or maladaptive repair process were investigated to predict reversibility of kidney injury. In the kidney of female F344 rats subjected to ischemia/reperfusion (I/R), regenerative tubules and dilated tubules were observed at 3 and 7 days after I/R. In fibrotic areas of the kidney of male SD rats subjected to I/R, renal tubules were dilated or atrophied. From microarray data of regenerative tubules, survivin, sex-determining region Y (SRY)-box 9 (SOX9), and CD44 were extracted as factors possibly relating to tubular regeneration or fibrosis. Immunohistochmical analysis demonstrated that survivin and SOX9 expressed in regenerative tubules, while SOX9 also expressed in renal tubules in fibrotic area, indicating that survivin and SOX9 contribute renal tubular regeneration, but sustained SOX9 expression may lead fibrosis. CD44 expressed in dilated tubules at day 3 and 7, and tubules in fibrotic area, suggesting that CD44 expressed in maladaptive tubules. These information will be helpful to consider reversibility of kidney injury.
2020-06-01 | GSE148420 | GEO
Project description:MicroRNAs (miRNAs) are endogenous small RNAs of 18–23 nucleotides that regulate gene expression. Recently, plasma miRNAs have been investigated as biomarkers for various diseases. In the present study, we assessed whether the miRNA expression profiles of tubular tissues could discriminate proximal tubule injury and diagnose acute kidney injury (AKI) and the renal tubular dysfunction without morphological changes.
2015-03-17 | GSE66195 | GEO
Project description:Multipotent progenitor cells (MPs) have been observed in human kidneys and particularly in Bowman's capsule and proximal tubules. The kidney owns the ability to repair local damage and renal MPs may play a role in the regenerative processes. Microarray technology was applied to identify differentially expressed genes among resident MPs isolated from glomeruli and tubules of normal renal tissue, renal proximal tubular epithelial cells (RPTECs) and mesenchymal stem cells (MSCs). The results of our analysis represent a starting point for further functional studies. Experiment Overall Design: This study includes three renal tissue samples which were processed to obtain 3 glomerular progenitor populations and 3 tubular ones. Three subcoltures of MSCs and RPTECs were included as well. The differences in gene expression patterns of the 4 cell types were found out.
2009-11-09 | E-GEOD-8611 | biostudies-arrayexpress
Project description:Retinoic acid (RA) signaling is activted in proximal tubular epithelial cells (PTECs) after acute kidney injury (AKI). In these studies we evaluated the functional role of this by inducing ischemia reperfusion-induced AKI (IRI-AKI) in mice after inhibiting RA signaling in PTECs genetically. Here we evaluated the effects of this on the activation of renal mononuclear cells (MNCs) by evaluating RNA expression in CD11B+ cells isolated from kidneys after IRI-AKI. Compared with control mice, there was a reducion in expression of inflammatory marker gene expression 3 days after IRI-AKI in mice with inhibition of RAR signaling in PTECs. These findings suggest a mechanism by which inhibition of RAR signaling in PTECs is protective against AKI.
2023-08-07 | GSE239850 | GEO
Project description:Renal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF. AKI in VHL-KO mice leads to prominent HIF activation in all nephron segments, as well as to reduced serum creatinine, serum urea, tubular necrosis, and apoptosis marker caspase-3 protein. At d1 after rhabdomyolysis, when tubular injury is potentially reversible, HIF mediated protection in AKI is associated with activated glycolysis, cellular glucose uptake and utilization, autophagy, vasodilation, and proton removal as demonstrated by qPCR, pathway enrichment analysis and immunohistochemistry. Together, our data provide evidence for a HIF-orchestrated multi-level shift towards glycolysis as a major mechanism for protection against acute tubular injury. All experiments were carried out in transgenic mice in which selective renal tubular VHL knockout (VHL-KO) was inducible by doxycycline (Reference: Mathia S, Paliege A, Koesters R, Peters H, Neumayer HH, Bachmann S, Rosenberger C. Action of hypoxia-inducible factor in liver and kidney from mice with Pax8-rtTA-based deletion of von Hippel-Lindau protein. Acta Physiol (Oxf). 2013; 207(3):565-76.). Four groups of animals were used: 1) controls: untreated mice; 2) VHL-KO: injected with doxycycline (0.1 mg per 10 g body weight SC), 4 days prior to sacrifice; 3) AKI: rhabdomyolysis; 4) VHL-KO/AKI: doxycycline plus rhabdomyolysis. To induce AKI, 50% glycerol (0.05 ml per 10 g body weight) was injected IM into the left hind limb under isoflurane narcosis. Drinking water was withdrawn between 20 h prior and 24 h after glycerol injection.
2013-09-05 | E-GEOD-44925 | biostudies-arrayexpress
Project description:Acute kidney injury (AKI) is a common clinical condition associated with diverse etiologies and abrupt loss of renal function. In patients with sepsis, rhabdomyolysis, cancer, as well as cardiovascular disorders, the underlying disease or associated therapeutic interventions can cause hypoxic, cytotoxic, and inflammatory insults to renal tubular epithelial cells (RTECs) resulting in the onset of AKI. To uncover stress-responsive disease-modifying genes, here we have carried out renal transcriptome profiling in three distinct murine models of AKI. We find that Vgf nerve growth factor inducible gene upregulation is a common transcriptional stress response in RTECs to ischemia, cisplatin, and rhabdomyolysis-associated renal injury. The Vgf gene encodes a secretory peptide precursor protein that has critical neuro-endocrine functions; however, its role in the kidneys remains unknown. Our functional studies show that RTEC-specific Vgf gene ablation exacerbates ischemia, cisplatin, and rhabdomyolysis-associated AKI in vivo and cisplatin-induced RTEC cell death in vitro. Importantly, addback experiments showed that aggravation of cisplatin-induced renal injury caused by Vgf gene ablation is partly reversed by TLQP-21, a Vgf-derived peptide. Finally, in vitro and in vivo mechanistic studies showed that injury-induced Vgf upregulation in RTECs is driven by the transcriptional regulator Sox9. These findings identify Vgf as an essential stress-responsive gene and reveal a crucial molecular target of the Sox9 regulated transcriptional program that controls epithelial cell fate during AKI.
2020-09-03 | GSE153625 | GEO