A Switch in Iron Transport Mechanisms Defines Novel Forms of Congenital Chronic Kidney Disease
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PROVIDER: PRJNA391158 | ENA |
REPOSITORIES: ENA
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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 | 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 | GSE100251 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-09-06 | GSE100254 | GEO
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:A Switch in Iron Transport Mechanisms Defines Novel Forms of Congenital Chronic Kidney Disease [P60 Tfr1KO KspCre]
| PRJNA391162 | ENA
Project description:Congenital heart disease (CHD) is the most frequent birth defect and affects nearly 1% of newborns. The etiology of CHD is largely unknown and only a small percentage can be assigned to environmental risk factors such as maternal diseases or exposure to mutagenic agents during pregnancy. Chromosomal imbalances have been identified in many forms of syndromic CHD, but next to nothing is known about the impact of DNA copy number changes in non-syndromic CHD. Here we present a sub-megabase resolution array CGH screen of a cohort with CHD as the sole abnormality at the time of diagnosis. Keywords: array CGH In this BAC array CGH study 104 patients with congenital heart disease and some of their parents were screened for DNA copy number changes at submegabase resolution. No dye swap was performed.
2008-05-11 | E-GEOD-7527 | biostudies-arrayexpress
Project description:Global gene expression analysis was performed comparing human skeletal muscle samples from patients with various forms of muscular dystrophy and mitochondrial myopathies in order to identify specific gene expression changes associated with collagen VI deficiency (leading to UllrichM-BM-4s Congenital Muscular Dystrophy) and depletion of mitochondrial DNA relative to other mitochondrial myopathies We analysed the gene expression profile of skeletal muscle from children suffering from mitochondrial myopathies and various forms of muscular dystrophy relative to skeletal muscle from healthy children using commercially available arrays that represents the complete human genome (Agilent Human SurePrintGE, 8x60K )
2015-01-20 | E-GEOD-43698 | biostudies-arrayexpress
Project description:Plants maintain iron (Fe) homeostasis under varying environmental conditions by balancing processes such as Fe uptake, transport, and storage. In Arabidopsis, POPEYE (PYE), a basic helix-loop-helix (bHLH) transcription factor (TF), has been shown to play a crucial role in regulating this balance. In recent years, the mechanisms regulating Fe uptake have been well established but the upstream transcriptional regulators of Fe transport and storage are still poorly understood. In this study, we report that ELONGATED HYPOCOTYL5 (HY5), a basic leucine zipper (bZIP) TF which has recently been shown to play a crucial role in Fe homeostasis, interacts with PYE. Molecular, genetic and biochemical approaches revealed that PYE and HY5 have overlapping as well as some distinct roles in regulation of Fe deficiency response. We found that HY5 and PYE both act as a repressor of Fe transport genes such as YSL3, FRD3, NPF5.9, YSL2, NAS4, and OPT3. HY5 was found to directly bind on the promoter of these genes and regulate intercellular Fe transport. Further analysis revealed that HY5 and PYE directly interact at the same region on PYE and NAS4 promoter. Overall, this study revealed that HY5 regulates Fe homeostasis by physically interacting with PYE as well as independently.
2024-09-02 | E-MTAB-14365 | biostudies-arrayexpress