scholarly journals Dissection of a genetic locus influencing renal function in the rat and its concordance with kidney disease loci on human chromosome 1q21

2007 ◽  
Vol 30 (3) ◽  
pp. 322-334 ◽  
Author(s):  
Michael R. Garrett ◽  
William T. Gunning ◽  
Tracy Radecki ◽  
Arti Richard
Keyword(s):  
Gene Expression ◽  
Renal Function ◽  
Kidney Disease ◽  
Human Chromosome ◽  
Pathway Analysis ◽  
Congenic Strain ◽  
Time Course ◽  
Chromosome 2 ◽  
Disease Loci ◽  
Chromosome 1Q21

Previously, we conducted a genome scan on a population derived from the Dahl salt-sensitive hypertensive (S) and the spontaneously hypertensive rat (SHR) using urinary albumin excretion (UAE) as our primary measure of renal function. We identified 10 quantitative trait loci (QTL) linked to several renal and/or cardiovascular traits. In particular, linkage and subsequent congenic strain analysis demonstrated that the loci on chromosome 2 had a large and significant effect on UAE compared with the S rat. The present work sought to characterize the chromosome 2 congenic strain [S.SHR( 2 )] by conducting a time-course analysis ( week 4–20), including evaluating additional renal parameters, histology, electron microscopy, and gene expression/ pathway analysis. Throughout the time course the congenic strain consistently maintained a threefold reduction in UAE compared with S rats and was supported by the histological findings of significantly reduced glomerular, tubular and interstitial changes. Gene expression/pathway analysis performed at week 4, 12, and 20 revealed that pathways involved in cellular assembly and organization, cellular movement, and immune response were controlled differently between the S and congenic. When all the data are considered, the chromosome 2 congenic appears to attenuate renal damage primarily through an altered fibrotic response. Recombinant progeny testing was employed to reduce the QTL to ∼1.5 cM containing several interesting candidate genes. The concordance of this rat QTL with renal disease loci on human chromosome 1q21 demonstrate that elucidating the causative gene and mechanism of the rat QTL may be of particular importance for understanding kidney disease in humans.

scholarly journals Magnesium Attenuates Phosphate-Induced Deregulation of a MicroRNA Signature and Prevents Modulation of Smad1 and Osterix during the Course of Vascular Calcification

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Loïc Louvet ◽  
Laurent Metzinger ◽  
Janine Büchel ◽  
Sonja Steppan ◽  
Ziad A. Massy
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Smooth Muscle ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Inorganic Phosphate ◽  
Time Course ◽  
Mechanistic Explanation ◽  
High Phosphate

Vascular calcification (VC) is prevalent in patients suffering from chronic kidney disease (CKD). High phosphate levels promote VC by inducing abnormalities in mineral and bone metabolism. Previously, we demonstrated that magnesium (Mg2+) prevents inorganic phosphate- (Pi-) induced VC in human aortic vascular smooth muscle cells (HAVSMC). As microRNAs (miR) modulate gene expression, we investigated the role of miR-29b, -30b, -125b, -133a, -143, and -204 in the protective effect of Mg2+on VC. HAVSMC were cultured in the presence of 3 mM Pi with or without 2 mM Mg2+chloride. Total RNA was extracted after 4 h, 24 h, day 3, day 7, and day 10. miR-30b, -133a, and -143 were downregulated during the time course of Pi-induced VC, whereas the addition of Mg2+restored (miR-30b) or improved (miR-133a, miR-143) their expression. The expression of specific targets Smad1 and Osterix was significantly increased in the presence of Pi and restored by coincubation with Mg2+. As miR-30b, miR-133a, and miR-143 are negatively regulated by Pi and restored by Mg2+with a congruent modulation of their known targets Runx2, Smad1, and Osterix, our results provide a potential mechanistic explanation of the observed upregulation of these master switches of osteogenesis during the course of VC.

scholarly journals Early Changes in Gene Expression Profiles in AML Patients During Induction Chemotherapy

2021 ◽  
Author(s):  
Ingrid Jakobsen ◽  
Max Sundkvist ◽  
Niclas Björn ◽  
Henrik Gréen ◽  
Kourosh Lotfi
Keyword(s):  
Gene Expression ◽  
Complete Remission ◽  
Treatment Response ◽  
Induction Chemotherapy ◽  
Pathway Analysis ◽  
Time Course ◽  
Treatment Initiation ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Data Quality Control

Abstract Background: Elucidation of the genetic mechanisms underlying treatment response to standard induction chemotherapy in AML patients is warranted, in order to aid in risk-adapted treatment decisions as novel treatments are emerging. In this pilot study, we explored the treatment-induced expression patterns in a small cohort of AML patients by analyzing differential gene expression (DGE) over the first two days of induction chemotherapy.Methods: Blood samples were collected from ten AML patients at baseline (before treatment initiation) and during the first two days of treatment (Day 1; approximately 24 h, and Day 2; approximately 48 h after treatment initiation, respectively) and RNA was extracted for subsequent RNA sequencing. DGE between time points were assessed by pairwise analysis using the R package edgeR version 3.18.1 in all patients as well as in relation to treatment response (complete remission, CR, vs non-complete remission, nCR). Ingenuity Pathway Analysis (Qiagen) software was used for pathway analysis and visualization.Results: After initial data quality control, two patients was excluded from further analysis, resulting in a final cohort of eight patients with data from all three timepoints. DGE analysis demonstrated activation of pathways with genes directly or indirectly associated with NF-κB signaling. Significant activation of the NF-κB pathway was seen in 50% of the patients two days after treatment start, while iNOS pathway effects could be identified already after one day. nCR patients displayed activation of pathways associated with cell cycle progression, oncogenesis and anti-apoptotic behavior, including the STAT3 pathway and Salvage pathways of pyrimidine ribonucleotides. Notably, a significant induction of cytidine deaminase, an enzyme responsible for the deamination of Ara-C, could be observed between baseline and Day 2 in the nCR patients but not in patients achieving CR.Conclusions: In conclusion, we show that time-course analysis of gene expression represents a feasible approach to identify relevant pathways affected by standard induction chemotherapy in AML patients. This poses as a potential method for elucidating new drug targets and biomarkers for categorizing disease aggressiveness and evaluating treatment response. However, more studies on larger cohorts are warranted to elucidate the transcriptional basis for drug response.

Extinction of Albumin Gene Expression in a Panel of Human Chromosome 2 Microcell Hybrids

Genomics ◽  
1996 ◽  
Vol 31 (3) ◽  
pp. 348-358 ◽  
Author(s):  
Karen M. Cerosaletti ◽  
R.E.K. Fournier
Keyword(s):  
Gene Expression ◽  
Human Chromosome ◽  
Chromosome 2 ◽  
Albumin Gene ◽  
Microcell Hybrids

Neonatal dexamethasone administration causes progressive renal damage due to induction of an early inflammatory response

2008 ◽  
Vol 294 (4) ◽  
pp. F768-F776 ◽  
Author(s):  
Yan Liu ◽  
Harry van Goor ◽  
Rick Havinga ◽  
Julius F. W. Baller ◽  
Vincent W. Bloks ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Function ◽  
Time Course ◽  
Renal Damage ◽  
Premature Death ◽  
Later Life ◽  
Male Rats ◽  
Renal Deterioration ◽  
Fibrotic Process ◽  
Time Course Study

Glucocorticoids (GCs) are widely used to prevent chronic lung disease in immature newborns. Emerging evidence indicates that GC exposure in early life may interfere with kidney function and is associated with hypertension in later life. In this study, we have investigated the effect of neonatal dexamethasone (DEX) administration on renal function in rats. Male rats were treated with DEX in the first 3 days after birth, controls received saline (SAL). Severe renal damage associated with premature death was found at 50 wks upon DEX treatment, while renal function and morphology were normal in controls. A subsequent time-course study was performed from 2 days to 32 wks. Compared with controls, neonatal DEX administration led to significant and persistent growth retardation. Progressive proteinuria and increased systolic blood pressure were found from 8 wks onwards in DEX-treated animals. Renal α-SMA gene expression was elevated from wk 24 onwards and morphological fibrosis was noted at 32 wks of age following DEX treatment. Markedly increased renal gene expression of TNF-α and MCP-1 in DEX -treated rats was observed at day 7, probably contributing to the permanent increase in interstitial macrophage numbers that started at 14 days. Permanently elevated renal TGF-β gene expression was induced by DEX administration from 4 wks onwards. Our data indicate that neonatal DEX administration in rats leads to renal failure in later life, presumably due to an early inflammatory trigger that elicits a persistent pro-fibrotic process that eventually results in progressive renal deterioration.

scholarly journals Early Changes in Gene Expression Profiles in AML Patients During Induction Chemotherapy

2021 ◽  
Author(s):  
Ingrid Jakobsen ◽  
Max Sundkvist ◽  
Niclas Björn ◽  
Henrik Gréen ◽  
Kourosh Lotfi
Keyword(s):  
Gene Expression ◽  
Complete Remission ◽  
Treatment Response ◽  
Induction Chemotherapy ◽  
Pathway Analysis ◽  
Time Course ◽  
Treatment Initiation ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Data Quality Control

Abstract Background: Elucidation of the genetic mechanisms underlying treatment response to standard induction chemotherapy in AML patients is warranted, in order to aid in risk-adapted treatment decisions as novel treatments are emerging. In this pilot study, we explored the treatment-induced expression patterns in a small cohort of AML patients by analyzing differential gene expression (DGE) over the first two days of induction chemotherapy.Methods: Blood samples were collected from ten AML patients at baseline (before treatment initiation) and during the first two days of treatment (Day 1; approximately 24 h, and Day 2; approximately 48 h after treatment initiation, respectively) and RNA was extracted for subsequent RNA sequencing. DGE between time points were assessed by pairwise analysis using the R package edgeR version 3.18.1 in all patients as well as in relation to treatment response (complete remission, CR, vs non-complete remission, nCR). Ingenuity Pathway Analysis (Qiagen) software was used for pathway analysis and visualization.Results: After initial data quality control, two patients was excluded from further analysis, resulting in a final cohort of eight patients with data from all three timepoints. DGE analysis demonstrated activation of pathways with genes directly or indirectly associated with NF-κB signaling. Significant activation of the NF-κB pathway was seen in 50% of the patients two days after treatment start, while iNOS pathway effects could be identified already after one day. nCR patients displayed activation of pathways associated with cell cycle progression, oncogenesis and anti-apoptotic behavior, including the STAT3 pathway and Salvage pathways of pyrimidine ribonucleotides. Notably, a significant induction of cytidine deaminase, an enzyme responsible for the deamination of Ara-C, could be observed between baseline and Day 2 in the nCR patients but not in patients achieving CR.Conclusions: In conclusion, we show that time-course analysis of gene expression represents a feasible approach to identify relevant pathways affected by standard induction chemotherapy in AML patients. This poses as a potential method for elucidating new drug targets and biomarkers for categorizing disease aggressiveness and evaluating treatment response. However, more studies on larger cohorts are warranted to elucidate the transcriptional basis for drug response.

EFFECTIVENESS OF ANTIAGGREGANT THERAPY ON KIDNEY ACTIVITY IN THE PREDIALYSIS STAGE OF CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 6 (1) ◽  
pp. 55-60
Author(s):  
Khabib Barnoev ◽  
◽  
Sherali Toshpulatov ◽  
Nozima Babajanova ◽  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Comparative Study ◽  
Functional Status ◽  
Stage Ii ◽  
Term Administration ◽  
Antiaggregant Therapy

The article presents the results of a study to evaluate the effectiveness of antiaggregant therapy on the functional status of the kidneys in 115 patients with stage II and III chronic kidney disease on the basis of a comparative study of dipyridamole and allthrombosepin. Studies have shown that long-term administration of allthrombosepin to patients has led to improved renal function.

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