Grainyhead-like 2 influences renal cyst growth in a mouse model
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA864781 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20730957_1.fastq.gz | Fastqsanger.gz | |||
| SRR20730957_2.fastq.gz | Fastqsanger.gz | |||
| SRR20730958_1.fastq.gz | Fastqsanger.gz | |||
| SRR20730958_2.fastq.gz | Fastqsanger.gz | |||
| SRR20730959_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:To characterize GRHL2 as a potential progression modifier and therapeutic target in autosomal-dominant polycystic kidney disease.
2023-09-12 | GSE210217 | GEO
Project description:The Pkd1 gene was inactivated by tamoxifen at postnatal day 30 (P30) to generate a chronic-onset conditional Pkd1 gene knockout mouse model. Without any intervention, micro cysts could be detected adjacent to renal medulla-corticomedullary junction in Pkd1-/- mice until P180 and cystic phenotype is severe at P300. However, under dehydration situation, the cyst growth was more accelerated and progressive. The dehydration protocol resulted in Pkd1-/- mice varying degrees of sweating and weight loss. Mice that were not provided water during the day (water at night (D-WAN)) and mice that had access to water during the day (water all time (D-WAT)) showed significantly more weight loss compared with the control Pkd1-/- mice, although they drank more water at night. Interestingly, although D-WAN Pkd1-/- mice and D-WAT Pkd1-/- mice lost approximately body weights after one-day dehydration, while cyst enlargement and renal dysfunction was much more severe in the D-WAN Pkd1-/- mice after two-month intervention.
2021-04-27 | E-MTAB-10449 | biostudies-arrayexpress
Project description:Polycystic Kidney Disease is characterized by the formation of large fluid-filled cysts that eventually destroy the renal parenchyma leading to end-stage renal failure. Although remarkable progress has been made in understanding the pathologic mechanism of the disease, the precise orchestration of the early events leading to cyst formation is still unclear. Abnormal cellular proliferation was traditionally considered to be one of the primary irregularities leading to cyst initiation and growth. Consequently, many therapeutic interventions have focused on targeting this abnormal proliferation, and some have even progressed to clinical trials. However, the role of proliferation in cyst development was primarily examined at stages where cysts are already visible in the kidneys and therefore at later stages of disease development. In this study we focused on the cystic phenotype since birth in an attempt to clarify the temporal contribution of cellular proliferation in cyst development. Using a PKD2 transgenic rat model (PKD2 (1-703)) of different ages (0-60 days after birth) we performed gene expression profiling and phenotype analysis by measuring various kidney parameters. Phenotype analysis demonstrated that renal cysts appear immediately after birth in the PKD2 transgenic rat model (PKD2 (1-703)). On the other hand, abnormal proliferation occurs at later stages of the disease as identified by gene expression profiling. Interestingly, other pathways appear to be deregulated at early stages of the disease in this PKD model. Our data suggest that cystogenesis precedes deregulation of proliferation-related pathways, suggesting that proliferation abnormalities may contribute in cyst growth rather than cyst formation. In this study we focused on the cystic phenotype since birth in an attempt to clarify the temporal contribution of cellular proliferation in cyst development. Using a PKD2 transgenic rat model (PKD2 (1-703)) of different ages (0,6 and 24 days after birth) we performed gene expression profiling of kidney cells.
2010-01-31 | E-GEOD-19460 | biostudies-arrayexpress
Project description:Kidney cyst formation occurs due to loss of cilia localized polycystin proteins (e.g., Pkd1 or Pkd2) or ciliary structure (e.g., Ift88 or Kif3a). However, cyst progression is more rapid in polycystin mutant mice compared to cilia mutant mice, and loss of cilia in the polycystin mutant background (e.g., Pkd2 and Kif3a mutation) greatly attenuates cyst development. This led to the proposal that the polycystins function to repress a cyst promoting pathway that is dependent on an intact cilium. Renal macrophages are also involved in regulating cyst progression, and the macrophage accumulation paralles with cyst expansion. but it is unknown whether this occurs through a cilia-dependent pathway or the consequence of cyst expansion. To address this question, we compared macrophage accumulation level and phenotypes in cystic kidneys from Pc2 mutant and Ift88; Pkd2 double mutant mice by prefromed 10x Genomics scRNAseq techniques. And to avoid the varying cyst severity in these mouse from different mutations, the cystic kidneys from Pc2 mutant and Ift88; Pkd2 double mutant mice were collected by adjusting for cystic indices rather than age.
2025-05-27 | GSE297737 | GEO
Project description:Polycystic Kidney Disease is characterized by the formation of large fluid-filled cysts that eventually destroy the renal parenchyma leading to end-stage renal failure. Although remarkable progress has been made in understanding the pathologic mechanism of the disease, the precise orchestration of the early events leading to cyst formation is still unclear. Abnormal cellular proliferation was traditionally considered to be one of the primary irregularities leading to cyst initiation and growth. Consequently, many therapeutic interventions have focused on targeting this abnormal proliferation, and some have even progressed to clinical trials. However, the role of proliferation in cyst development was primarily examined at stages where cysts are already visible in the kidneys and therefore at later stages of disease development. In this study we focused on the cystic phenotype since birth in an attempt to clarify the temporal contribution of cellular proliferation in cyst development. Using a PKD2 transgenic rat model (PKD2 (1-703)) of different ages (0-60 days after birth) we performed gene expression profiling and phenotype analysis by measuring various kidney parameters. Phenotype analysis demonstrated that renal cysts appear immediately after birth in the PKD2 transgenic rat model (PKD2 (1-703)). On the other hand, abnormal proliferation occurs at later stages of the disease as identified by gene expression profiling. Interestingly, other pathways appear to be deregulated at early stages of the disease in this PKD model. Our data suggest that cystogenesis precedes deregulation of proliferation-related pathways, suggesting that proliferation abnormalities may contribute in cyst growth rather than cyst formation.
2010-02-01 | GSE19460 | GEO
Project description:Melanin-like nanoparticles (MNPs) have recently emerged as valuable agents in antioxidant therapy due to their excellent biocompatibility and potent capacity to scavenge various reactive oxygen species (ROS). However, previous studies have mainly focused on acute ROS-related diseases, leaving a knowledge gap regarding their potential in chronic conditions. Furthermore, apart from their well-established antioxidant effects, it remains unclear whether MNPs target other intracellular molecular pathways. In this study, we synthesized ultra-small polyethylene glycol-incorporated Mn2+-chelated MNP (MMPP). We discovered that MMPP traversed the glomerular filtration barrier and specifically accumulated in renal tubules. Autosomal dominant polycystic kidney disease (ADPKD) is a chronic genetic disorder closely associated with increased oxidative stress and featured by the progressive enlargement of cysts originating from various segments of the renal tubules. Treatment with MMPP markedly attenuated oxidative stress levels, inhibited cyst growth, thereby improving renal function. Interestingly, we found that MMPP effectively inhibits a cyst-promoting gene program downstream of the cAMP-CREB pathway, a crucial signaling pathway implicated in ADPKD progression. Mechanistically, we observed that MMPP directly binds to the bZIP DNA-binding domain of CREB, leading to competitive inhibition of CREB's DNA binding ability and subsequent reduction in CREB target gene expression. Furthermore, by engineering an orally administrable formulation, we demonstrated that orally delivered-MMPP also effectively inhibits cyst growth. In summary, our findings highlight the potential of MMPP in delaying the progression of ADPKD by simultaneously targeting oxidative stress and CREB transcriptional activity.
2024-10-10 | GSE235269 | GEO
Project description:Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and
PKD2, encoding polycystin-1 (PC1) and polycystin-2 (PC2), which are required for the regulation
of the renal tubular diameter. Loss of polycystin function results in cyst formation. Atypical forms
of ADPKD are caused by mutations in genes encoding endoplasmic reticulum (ER)-resident
proteins through mechanisms that are not well understood. Here, we investigate the function of
DNAJB11, an ER co-chaperone associated with atypical ADPKD. We generated mouse models with
constitutive and conditional Dnajb11 inactivation and Dnajb11-deficient renal epithelial cells to
investigate the mechanism underlying autosomal dominant inheritance, the specific cell types
driving cyst formation, and molecular mechanisms underlying DNAJB11-dependent polycystic
kidney disease. We show that biallelic loss of Dnajb11 causes cystic kidney disease and fibrosis,
mirroring human disease characteristics. In contrast to classical ADPKD, cysts predominantly
originate from proximal tubules. Cyst formation begins in utero and the timing of Dnajb11
inactivation strongly influences disease severity. Furthermore, we identify impaired PC1 cleavage
as a potential mechanism underlying DNAJB11-dependent cyst formation. Proteomic analysis of
Dnajb11- and Pkd1-deficient cells reveals common and distinct pathways and dysregulated
proteins, providing a foundation to better understand phenotypic differences between different
forms of ADPKD.
| MSV000095951 | MassIVE
Project description:Autosomal dominant polycystic kidney disease (ADPKD) is caused by muta1ons in PKD1 and
PKD2, encoding polycystin-1 (PC1) and polycystin-2 (PC2), which are required for the regula1on
of the renal tubular diameter. Loss of polycystin func1on results in cyst forma1on. Atypical forms
of ADPKD are caused by mutations in genes encoding endoplasmic reticulum (ER)-resident
proteins through mechanisms that are not well understood. Here, we investigate the func1on of
DNAJB11, an ER co-chaperone associated with atypical ADPKD. We generated mouse models with
constitutive and conditional Dnajb11 inactivation and Dnajb11-deficient renal epithelial cells to
investigate the mechanism underlying autosomal dominant inheritance, the specific cell types
driving cyst formation, and molecular mechanisms underlying DNAJB11-dependent polycystic
kidney disease. We show that biallelic loss of Dnajb11 causes cystic kidney disease and fibrosis,
mirroring human disease characteristics. In contrast to classical ADPKD, cysts predominantly
originate from proximal tubules. Cyst formation begins in utero and the timing of Dnajb11
inactivation strongly influences disease severity. Furthermore, we identify impaired PC1 cleavage as a potential mechanism underlying DNAJB11-dependent cyst formation. Proteomic analysis of Dnajb11- and Pkd1-deficient cells reveals common and distinct pathways and dysregulated proteins, providing a foundation to better understand phenotypic differences between different forms of ADPKD.
| MSV000095950 | MassIVE
Project description:Fumarate hydratase (FH) mutations predispose to renal cysts cancer. These cancers overexpress hypoxia-inducible factor-alpha (Hif-1a). We have generated a conditional Fh1 (mouse FH) knockout mice that develop renal cysts and overexpress Hif-1a. In order to identify the contribution of Hif-1a to cyst formation we have intercrossed our mice with conditional HIf-1a KO mice. We intercrossed Fh1/Hif1a mice with kidney specific cre recombinase (Ksp-Cre) and analysed kidney cyst formation. RNA was extracted from cysts from 4xFh1 KO, 4xFh1/Hif-1a KO and 4 control mice. For each comparison littermates were used and the animals were aged 15 weeks i.e. early cystic disease.
2011-10-23 | E-GEOD-29988 | biostudies-arrayexpress
Project description:To elucidate the systems biology of miRNAs in human PKD1 renal cyst growth
2022-01-23 | GSE133530 | GEO