Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1217615 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32187735.fastq.gz | Fastqsanger.gz | |||
| SRR32187736.fastq.gz | Fastqsanger.gz | |||
| SRR32187737_1.fastq.gz | Fastqsanger.gz | |||
| SRR32187737_2.fastq.gz | Fastqsanger.gz | |||
| SRR32187738_1.fastq.gz | Fastqsanger.gz |
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Project description:Gene expression profiling of kidneys from the murine model of HIV-associated nephropathy (HIVAN) identified an association between the expression of an endoplasmic reticulum (ER)-associated protein reticulon-1, RTN1, and the severity of kidney disease. Of the three known RTN1 isoforms, only RTN1A protein expression was increased in kidneys of murine models of HIVAN, diabetic nephropathy (DN), and renal fibrosis and humans with HIVAN and DN. Both mRNA and protein expression of RTN1-A in the kidneys correlated inversely with estimated glomerular filtration rate (eGFR) in patients with DN. In kidney cells, RTN1 overexpression induced ER stress/apoptosis, whereas RTN1 knockdown attenuated tunicamycin-, and hyperglycemia-induced ER stress/apoptosis. Incubation of kidney cells with high glucose media induced RTN1A expression likely through oxidative pathway, while knockdown of RTN1A inhibited high glucose-induced apoptosis. RTN1A interacts with PERK and mutation of its N- or C-terminal domain abolished its effects on ER stress/apoptosis. In vivo, knockdown of Rtn1a expression either before or after kidney injury attenuated renal fibrosis in mice with unilateral ureteral obstruction (UUO) and tubular epithelial cell-specific knockdown of Rtn1a also ameliorated ER stress and renal fibrosis in the UUO mice. Finally, knockdown of Rtn1a also attenuated proteinuria, glomerular hypertrophy, and mesangial expansion in STZ-induced diabetic mice, which were associated with suppression of ER stress markers. Taken together, these data suggest that RTN1 is a mediator of kidney disease progression that exacerbates kidney injury through ER stress and apoptosis. Animal studies: All animal studies were approved by the IACUC committee of Mount Sinai School of Medicine. HIV-1 transgenic mice, Tg26, and their littermates were generated and genotyped as described. Only male heterozygous Tg26 in the FVB/N background were used in the study, because homozygous HIV-transgenic mice are not viable for more than few weeks postnatally. UUO and folic acid-induced nephropathy models were created as described . Mice were grouped as wild type, Tg26 with mild kidney injury, Tg26, with serious kidney injury. The kidneys were collected from these mice for histology, western blot, real-time PCR analysis, and microarray studies. Kidney disease was confirmed by measurement of proteinuria, renal function, and histologic analysis. Microarray studies: Affymetrix gene expression microarrays were performed at the Mount Sinai Institution Microarray Core Facility. The Affymetrix GeneChip® Mouse Genome 430 2.0 Array was used to profile gene expression in the kidney cortex of Tg26 and WT mice 37. One-way analysis of variance test (ANOVA) was applied to the dataset to identify the genes that were differentially expressed between the two groups. P-values were corrected using Benjamini–Hochberg false discovery rate (FDR) with a threshold of 0.05.
2015-05-20 | E-GEOD-69074 | biostudies-arrayexpress
Project description:Gene expression profiling of kidneys from the murine model of HIV-associated nephropathy (HIVAN) identified an association between the expression of an endoplasmic reticulum (ER)-associated protein reticulon-1, RTN1, and the severity of kidney disease. Of the three known RTN1 isoforms, only RTN1A protein expression was increased in kidneys of murine models of HIVAN, diabetic nephropathy (DN), and renal fibrosis and humans with HIVAN and DN. Both mRNA and protein expression of RTN1-A in the kidneys correlated inversely with estimated glomerular filtration rate (eGFR) in patients with DN. In kidney cells, RTN1 overexpression induced ER stress/apoptosis, whereas RTN1 knockdown attenuated tunicamycin-, and hyperglycemia-induced ER stress/apoptosis. Incubation of kidney cells with high glucose media induced RTN1A expression likely through oxidative pathway, while knockdown of RTN1A inhibited high glucose-induced apoptosis. RTN1A interacts with PERK and mutation of its N- or C-terminal domain abolished its effects on ER stress/apoptosis. In vivo, knockdown of Rtn1a expression either before or after kidney injury attenuated renal fibrosis in mice with unilateral ureteral obstruction (UUO) and tubular epithelial cell-specific knockdown of Rtn1a also ameliorated ER stress and renal fibrosis in the UUO mice. Finally, knockdown of Rtn1a also attenuated proteinuria, glomerular hypertrophy, and mesangial expansion in STZ-induced diabetic mice, which were associated with suppression of ER stress markers. Taken together, these data suggest that RTN1 is a mediator of kidney disease progression that exacerbates kidney injury through ER stress and apoptosis.
2015-05-20 | GSE69074 | GEO
Project description:Lipid mal-metabolism, particularly fatty acid oxidation (FAO) dysfunction, is a major driver of renal fibrosis. However, detailed regulatory mechanisms underlying this process remain unclear. In this study, we demonstrated that acyl-CoA thioesterase 12 (Acot12) is a key regulator of lipid metabolism in fibrotic kidneys. A significantly decreased level of ACOT12 was observed in a kidney sample of human patients with chronic kidney disease as well as in mouse kidney injury. Acot12 deficiency induces lipid accumulation and fibrosis in mice subjected to unilateral ureteral obstruction (UUO). Fenofibrate administration does not reduce renal fibrosis in Acot12-/- mice with UUO. Moreover, restoration of peroxisome proliferator-activated receptor (PPAR in Acot12-/- Ppar-/- kidneys with UUO exacerbated lipid accumulation and renal fibrosis, whereas restoration of Acot12 in Acot12-/- Ppar-/- kidneys with UUO significantly reduced lipid accumulation and renal fibrosis suggesting, mechanistically, Acot12 deficiency exacerbates renal fibrosis independently of PPAR. In Acot12-/- kidneys with UUO, a reduction in the selective autophagic degradation of peroxisomes and pexophagy with a decreased level of ACBD5 was observed. In conclusion, our study demonstrates the functional role and mechanistic details of Acot12 in the progression of renal fibrosis, provides a preclinical rationale for regulating Acot12 expression and presents a novel means of preventing renal fibrosis.
2025-03-12 | GSE261115 | GEO
Project description:Numerous studies have proven the critical role of macrophages in the renal fibrosis process. Notably, G Protein-coupled Estrogen Receptor 1 (GPER1), a novel estrogen receptor, has been shown to play a ubiquitous role in the regulation of macrophage activities and proinflammatory pathways. However, the precise role of GPER1 in macrophage-mediated renal fibrosis is unknown. In this study, we aimed to investigate the function of macrophage GPER1 in the UUO-induced renal fibrosis model. Compared to vehicle-treated ovariectomized (OVX) female and male UUO models, we observed that G-1 (GPER1 agonist)-treated OVX female and male UUO mice had fewer renal fibrotic lesions and less M1 and M2 macrophage infiltration in the kidney tissues. Conversely, Gper1 deletion in male UUO mice accelerated renal fibrosis and increased inflammation. In vitro studies also revealed that GPER1 activation reduced M0 macrophage polarization towards M1 and M2 phenotypes. The RNA sequencing analysis and immunoblotting indicated that GPER1 activation was primarily involved in downregulating immune pathways activation and inactivating MAPK pathways. Tubular epithelial cells co-cultured with G1-pretreated M1 macrophages exhibited fewer injuries and immune activation. In addition, fibroblasts co-cultured with G1-pretreated M2 macrophages showed downregulated extracellular matrix expression. Overall, this is the first study to demonstrate the effect of GPER1 on macrophage-mediated renal fibrosis via inhibition of M1 and M2 macrophage polarization. These findings indicate that GPER1 may be a promising therapeutic target for the treatment of renal fibrosis.
2023-12-20 | GSE235718 | GEO
Project description:In this study, we employed high-throughput RNA sequencing (RNA-Seq) to identify the Smad3-dependent lncRNAs related to renal inflammation and fibrosis in Smad3 knockout (KO) mouse models of unilateral ureteral obstructive nephropathy (UUO) and immunologically-induced anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). 12 kidney tissue samples of Smad3 KO/WT mice from normal control, UUO at day 5 or anti-GBM GN at day 10 models (n=2 in each group) for whole transcriptome RNA-sequencing.
2014-03-26 | E-GEOD-55808 | biostudies-arrayexpress
Project description:Oral administration of Si-based agents produces large amounts of hydrogen under alkaline conditions in the intestinal tract. Hydrogen removes reactive oxygen species and reduces oxidative stress. It is also known that oxidative stress is involved in the progression of renal fibrosis. We reported that oral administration of Si- based agent suppressed renal fibrosis using UUO model. mRNA expression in Sham group, UUO group, and UUO+Si group was evaluated by RNA-seq and functional analysis, and found that fibrosis-related Gene ontology and Pathways related to fibrosis were suppressed by the Si-based agent.
2025-03-02 | GSE261665 | GEO
Project description:Renal fibrosis as the final outcome of many renal diseases, has always been paid more attention to by the researchers. To better understand whether lncRNAs could be a player in this process or be a biomarker for renal fibrosis diagnosis, we compared transcriptome sequencing data on renal tissues and urine respectively between UUO and shamed (Sham) rat model. Numerous genes including lncRNAs with significant changes in their expression were identified. 24 lncRNAs were up-regulated and 79 lncRNAs were down-regulated in the renal tissues of the UUO rats. 625 lncRNAs were up-regulated and 177 lncRNAs were down-regulated in urines of the UUO rats. Among the lncRNAs upregulated in renal tissue of UUO rats, 19 lncRNAs were predicted containing several conserved Smad3 binding motifs in the promoter. Among them, lncRNAs with putative promoter containing more than 4 conserved Smad3 binding motifs were demonstrated to be induced by TGF-β significantly in NRK-52E cells. We further confirmed that lncRNA TCONS_00088786 and TCONS_01496394 were regulated by TGF-β stimulation and also can influence the expression of some fibrosis-related genes through a feedback loop. Based on transcriptome sequencing data, bioinformatics analysis and qRT-PCR detection, we also demonstrated lncRNA in Urine are detectable and might be a novel biomarker of renal fibrosis. These data provide new information about the involvement of lncRNAs in renal fibrosis, indicating that they may serve as candidate biomarkers or therapeutic targets in the future.
2017-08-12 | GSE100632 | GEO
Project description:Renal fibrosis as the final outcome of many renal diseases, has always been paid more attention to by the researchers. To better understand whether lncRNAs could be a player in this process or be a biomarker for renal fibrosis diagnosis, we compared transcriptome sequencing data on renal tissues and urine respectively between UUO and shamed (Sham) rat model. Numerous genes including lncRNAs with significant changes in their expression were identified. 24 lncRNAs were up-regulated and 79 lncRNAs were down-regulated in the renal tissues of the UUO rats. 625 lncRNAs were up-regulated and 177 lncRNAs were down-regulated in urines of the UUO rats. Among the lncRNAs upregulated in renal tissue of UUO rats, 19 lncRNAs were predicted containing several conserved Smad3 binding motifs in the promoter. Among them, lncRNAs with putative promoter containing more than 4 conserved Smad3 binding motifs were demonstrated to be induced by TGF-β significantly in NRK-52E cells. We further confirmed that lncRNA TCONS_00088786 and TCONS_01496394 were regulated by TGF-β stimulation and also can influence the expression of some fibrosis-related genes through a feedback loop. Based on transcriptome sequencing data, bioinformatics analysis and qRT-PCR detection, we also demonstrated lncRNA in Urine are detectable and might be a novel biomarker of renal fibrosis. These data provide new information about the involvement of lncRNAs in renal fibrosis, indicating that they may serve as candidate biomarkers or therapeutic targets in the future.
2017-08-12 | GSE100631 | GEO
Project description:Chronic kidney disease is associated with progressive renal fibrosis, where perivascular cells give rise to the majority of α-SMA positive myofibroblasts. We sought to identify pericytic miRNAs that could serve as a target to decrease myofibroblast formation. We induced kidney fibrosis in FoxD1-GC;Z/Red-mice by unilateral ureteral obstruction (UUO) followed by FACS sorting of dsRed-positive FoxD1-derivative cells and miRNA profiling. MiR-132 selectively increased 21-fold during pericyte-to-myofibroblast formation whereas miR-132 was only 2.5-fold up in total kidney lysates (both in UUO and ischemia-reperfusion injury). MiR-132 silencing in UUO decreased collagen deposition (35%) and tubular apoptosis. Immunohistochemistry, western blot and qRT-PCR confirmed a similar decrease in interstitial α-SMA+ cells. Pathway analysis identified a rate-limiting role for miR-132 in myofibroblast proliferation that was confirmed in vitro. Indeed, antagomir-132 treated mice displayed a reduction in the number of proliferating, ki67+ interstitial myofibroblasts. Interestingly, this was selective for the interstitial compartment and did not impair the reparative proliferation of tubular epithelial cells, as evidenced by an increase in ki67+ epithelial cells, as well as increased (p-)RB1, Cyclin-A and decreased RASA1, p21 levels in kidney lysates. Taken together, silencing miR-132 counteracts the progression of renal fibrosis by selectively decreasing myofibroblast proliferation and could potentially serve as a novel antifibrotic therapy. Total RNA obtained from FACS sorted mouse renal FoxD1-derivatve interstitial cells from mice that were treated with antagomir-132 or scramblemir and underwent UUO (n=4)
2016-02-16 | E-GEOD-76548 | biostudies-arrayexpress
Project description:Renal fibrosis is a common consequence of various progressive nephropathies, including obstructive nephropathy, and ultimately leads to kidney failure. Infiltration of inflammatory cells is a prominent feature of renal injury after draining blockages from the kidney, and correlates closely with the development of renal fibrosis. However, the underlying molecular mechanism behind the promotion of renal fibrosis by inflammatory cells remains unclear. Herein, we showed that unilateral ureteral obstruction (UUO) induced Gasdermin D (GSDMD) activation in neutrophils, abundant neutrophil extracellular traps (NETs) formation and macrophage-to-myofibroblast transition (MMT) characterized by α-smooth muscle actin (α-SMA) expression in macrophages. Gsdmd deletion significantly reduced infiltration of inflammatory cells in the kidneys and inhibited NETs formation, MMT and thereby renal fibrosis. Chimera studies confirmed that Gsdmd deletion in bone marrow-derived cells, instead of renal parenchymal cells, provided protection against renal fibrosis. Further, specific deletion of Gsdmd in neutrophils instead of macrophages protected the kidney from undergoing fibrosis after UUO. Single-cell RNA sequencing identified robust crosstalk between neutrophils and macrophages. In vitro, GSDMD-dependent NETs triggered p65 translocation to the nucleus, which boosted the production of inflammatory cytokines and α-SMA expression in macrophages by activating TGF-β1/Smad pathway. In addition, we demonstrated that caspase-11, that could cleave GSDMD, was required for NETs formation and renal fibrosis after UUO. Collectively, our findings demonstrate that caspase-11/GSDMD-dependent NETs promote renal fibrosis by facilitating inflammation and MMT, therefore highlighting the role and mechanisms of NETs in renal fibrosis.
2024-04-19 | GSE264184 | GEO