Mus musculus
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ABSTRACT:
PROVIDER: PRJNA391162 | ENA |
REPOSITORIES: ENA
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Project description:A Switch in Iron Transport Mechanisms Defines Novel Forms of Congenital Chronic Kidney Disease
| PRJNA391158 | ENA
Project description:A Switch in Iron Transport Mechanisms Defines Novel Forms of Congenital Chronic Kidney Disease [P15 FeD]
| PRJNA391167 | ENA
Project description:A Switch in Iron Transport Mechanisms Defines Novel Forms of Congenital Chronic Kidney Disease [P13 Tfr1KO Six2Cre]
| PRJNA391166 | ENA
Project description:Periconceptual maternal iron deficiency (FeD) is a worldwide problem resulting in prematurity and low birth weights. Yet, it is not known whether FeD affects all developing tissues, or rather targets specific lineages. To address these questions, we investigated the targeting of the kidney by FeD. We found that FeD reduced both serum transferrin-iron and non-transferrin-bound-iron (NTBI), and these deficiencies targeted the renal proximal nephron rather than renal collecting ducts or stroma. In contrast, proximal tubular deletions of TfR1 (TfD) caused only modest defects in kidney development implying compensation by NTBI in the embryo. Yet, after the first two postnatal weeks, proximal TfD resulted in striking segmentally specific hypoplasia, as well as well as pervasive cystic transformation with Bardet-Biedel or Nephronothesis protein deficiencies. Treatment with NTBI as well as systemic activators of HIF which induce iron trafficking bypassed TfD and rescued the cystic disease and suppressed kidney damage. In sum, iron depletion resulted in new forms of chronic kidney disease. Its phenotype resulted from the alternative use of two different forms of iron, NTBI and Tf-iron at different stages and in different cells of the developing kidney.
2025-09-08 | GSE100253 | GEO
Project description:Periconceptual maternal iron deficiency (FeD) is a worldwide problem resulting in prematurity and low birth weights. Yet, it is not known whether FeD affects all developing tissues, or rather targets specific lineages. To address these questions, we investigated the targeting of the kidney by FeD. We found that FeD reduced both serum transferrin-iron and non-transferrin-bound-iron (NTBI), and these deficiencies targeted the renal proximal nephron rather than renal collecting ducts or stroma. In contrast, proximal tubular deletions of TfR1 (TfD) caused only modest defects in kidney development implying compensation by NTBI in the embryo. Yet, after the first two postnatal weeks, proximal TfD resulted in striking segmentally specific hypoplasia, as well as well as pervasive cystic transformation with Bardet-Biedel or Nephronothesis protein deficiencies. Treatment with NTBI as well as systemic activators of HIF which induce iron trafficking bypassed TfD and rescued the cystic disease and suppressed kidney damage. In sum, iron depletion resulted in new forms of chronic kidney disease. Its phenotype resulted from the alternative use of two different forms of iron, NTBI and Tf-iron at different stages and in different cells of the developing kidney.
2025-09-08 | GSE100252 | GEO
Project description:Periconceptual maternal iron deficiency (FeD) is a worldwide problem resulting in prematurity and low birth weights. Yet, it is not known whether FeD affects all developing tissues, or rather targets specific lineages. To address these questions, we investigated the targeting of the kidney by FeD. We found that FeD reduced both serum transferrin-iron and non-transferrin-bound-iron (NTBI), and these deficiencies targeted the renal proximal nephron rather than renal collecting ducts or stroma. In contrast, proximal tubular deletions of TfR1 (TfD) caused only modest defects in kidney development implying compensation by NTBI in the embryo. Yet, after the first two postnatal weeks, proximal TfD resulted in striking segmentally specific hypoplasia, as well as well as pervasive cystic transformation with Bardet-Biedel or Nephronothesis protein deficiencies. Treatment with NTBI as well as systemic activators of HIF which induce iron trafficking bypassed TfD and rescued the cystic disease and suppressed kidney damage. In sum, iron depletion resulted in new forms of chronic kidney disease. Its phenotype resulted from the alternative use of two different forms of iron, NTBI and Tf-iron at different stages and in different cells of the developing kidney.
2025-09-08 | GSE100251 | GEO
Project description:Systemic iron metabolism is disrupted in chronic kidney disease (CKD). However, little is known about local kidney iron homeostasis and its role in kidney fibrosis. Kidney-specific effects of iron therapy in CKD also remain elusive. Here, we elucidate the role of macrophage iron status in kidney fibrosis and demonstrate that it is a potential therapeutic target. In CKD, kidney macrophages exhibited depletion of labile iron pool (LIP) and induction of transferrin receptor 1, indicating intracellular iron deficiency. Low LIP in kidney macrophages was associated with their defective antioxidant response and proinflammatory polarization. Repletion of LIP in kidney macrophages through knockout of ferritin heavy chain (Fth1) reduced oxidative stress and mitigated fibrosis. Similar to Fth1 knockout, iron dextran therapy, through replenishing macrophage LIP, reduced oxidative stress, decreased the production of proinflammatory cytokines, and alleviated kidney fibrosis. Interestingly, iron markedly decreased TGF-β expression and suppressed TGF-β–driven fibrotic response of macrophages. Iron dextran therapy and FtH suppression had an additive protective effect against fibrosis. Adoptive transfer of iron-loaded macrophages alleviated kidney fibrosis, validating the protective effect of iron-replete macrophages in CKD. Thus, targeting intracellular iron deficiency of kidney macrophages in CKD can serve as a therapeutic opportunity to mitigate disease progression.
2023-02-01 | GSE221598 | GEO
Project description:With a global increase in chronic kidney disease patients, alternatives to dialysis and organ transplantation are needed. Stem cell-based therapies could be one possibility to treat chronic kidney disease. Here, we used multipotent urine-derived renal progenitor cells (UdRPCs) to study nephrogenesis. UdRPCs treated with the JNK inhibitor- AEG3482, displayed decreased proliferation and downregulated transcription of cell cycle-associated genes as well as the kidney progenitor markers -SIX2, CITED1, and SALL1. In addition, levels of activated SMAD2/3, which is associated with the maintenance of self-renewal in UdRPCs, were decreased. JNK inhibition resulted in less efficient oxidative phosphorylation and more lipid peroxidation via ferroptosis- an iron-dependent non-apoptotic cell death pathway linked to various forms of kidney disease. Our study reveals the importance of JNK signalling in maintaining self-renewal as well as protection against ferroptosis in SIX2-positive UdRPCs. We propose that UdRPCs can be used for modelling ferroptosis-induced kidney diseases.
2024-08-13 | GSE211892 | GEO
Project description:Hereditary hemochromatosis and transfusional iron overload are frequent clinical conditions associated with progressive iron accumulation in parenchymal tissues leading to eventual organ failure. We have discovered a novel mechanism to reverse iron overload by pharmacological modulation of the divalent metal transporter-1 (DMT-1). DMT-1 mediates intracellular iron transport during the transferrin cycle and apical iron absorption in the duodenum. Additional functions in iron handling in the kidney and liver are less well understood. We show that the L- type calcium-channel blocker nifedipine increases DMT-1 mediated cellular iron transport 10-to 100-fold at concentrations between 1-100 uM. Mechanistically, nifedipine causes this effect by prolongation of the activity of DMT-1 to transport iron. We show that nifedipine mobilizes iron from the liver of mice with primary and secondary iron overload, and enhances urinary iron excretion. Modulation of DMT-1 function by L-type calcium-channel blockers emerges a novel pharmacological concept to treat iron overload disorders.<br> <br> In this experiment mice were subjected to dietary iron overload before being treated with nifedipine at 5 ug/g bodyweight, or mock treated with the same volume of solvent.
2007-03-01 | E-MEXP-982 | biostudies-arrayexpress
Project description:Building upon a foundational Human Kidney resource, we present a comprehensive multi-modal atlas that defines spatially resolved versus unresolved repair states and mechanisms in human kidney disease. Homeostatic interactions between injured kidney epithelium and its surrounding milieu determine successful repair outcomes, while pathogenic signaling promotes unresolved inflammation and fibrosis leading to chronic disease. We integrated multiple single-cell and spatial modalities across ~700 samples from >350 patients (~250 research biopsies), analyzing ~1.7 million cells alongside complementary mouse multi-omic profiles spanning acute-to-chronic injury and aging (>300,000 cells) and spatial transcriptomic analysis of 150 human biopsies. This cross-species atlas delineates functional pathways and druggable targets across the nephron and defines gene regulatory networks and chromatin landscapes governing tubular, fibroblast, and immune cell transitions from injury to either recovery or failed repair states. We identified distinct cellular states associated with specific pathological features that show dynamic distributions between acute kidney injury (AKI) and chronic kidney disease (CKD), organized within unique spatial niches that reveal progression mechanisms from early injury to unresolved disease. Gene regulatory analyses prioritized key transcription factor activities (SOX4, SOX9, NFKB1, REL, KLFs) and their target networks establishing disease states and tissue microenvironments. These regulatory programs were directly linked to clinical outcomes, identifying molecular signatures of recovery and secreted biomarkers predictive of AKI-to-CKD progression, providing a key resource for therapeutic development and precision medicine approaches in kidney disease.
2025-10-09 | GSE308709 | GEO