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 PAMP-triggered Genetic Reprogramming Involves Widespread Alternative Transcription Initiation and an Immediate Transcription Factor Wave

2021 ◽  
Author(s):  
Axel Thieffry ◽  
Jette Bornholdt ◽  
Andrea Barghetti ◽  
Albin Sandelin ◽  
Peter Brodersen
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Transcription Initiation ◽  
Time Course ◽  
Cell Activity ◽  
Open Reading Frames ◽  
Immune State ◽  
Alternative Transcription ◽  
Time Course Study ◽  
Drive Gene

ABSTRACTImmune responses triggered by pathogen-associated molecular patterns (PAMPs) are key to pathogen defense, but drivers of the genetic reprogramming required to reach the immune state remain incompletely understood in plants. Here, we report a time-course study of the establishment of PAMP-triggered immunity (PTI) using cap analysis of gene expression (CAGE). Our results show that as much as 15% of all PAMP response genes display alternative transcription initiation. In several cases, use of alternative TSSs may be regulatory as it determines inclusion of target peptides or protein domains, or occurrence of upstream open reading frames (uORFs) in mRNA leader sequences. We also find that 60% of PAMP-response genes respond much earlier than previously thought. In particular, a previously unnoticed cluster of rapidly and transiently PAMP-induced genes is enriched in transcription factors whose functions, previously associated with biological processes as diverse as abiotic stress adaptation and stem cell activity, appear to converge on growth restriction. Furthermore, some examples of known potentiators of PTI, in one case under direct MAP kinase control, support the notion that the rapidly induced transcription factors could constitute direct links to PTI signaling pathways and drive gene expression changes underlying establishment of the immune state.

scholarly journals Association of Blood Pressure Trajectories in Early Life with Subclinical Renal Damage in Middle Age

2018 ◽  
Vol 29 (12) ◽  
pp. 2835-2846 ◽  
Author(s):  
Wenling Zheng ◽  
Jianjun Mu ◽  
Chao Chu ◽  
Jiawen Hu ◽  
Yu Yan ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Disease ◽  
Early Life ◽  
Renal Damage ◽  
Middle Age ◽  
Later Life ◽  
Stable Group ◽  
Factors Affecting ◽  
Group A

BackgroundAlthough high BP is one of the most important factors affecting renal function, whether longitudinal BP trajectories in early life course are associated with renal function damage in later life is unclear.MethodsTo investigate the correlation between BP trajectories from childhood to adulthood and renal function in middle age, we used group-based trajectory models to identify BP trajectories in 2430 individuals (aged 6–15 years old at baseline) participating in the ongoing Hanzhong Adolescent Hypertension Cohort. We tested the association between these trajectories and subclinical renal damage in middle age, adjusting for several covariates.ResultsWe identified four distinct systolic BP trajectories among 2430 subjects: low stable, moderate stable, high stable, and moderate increasing on the basis of systolic BP levels at baseline and during the 30-year follow-up period. The urinary albumin-to-creatinine ratio (uACR) was higher in moderate stable, high stable, and moderate increasing groups compared with the low stable group. A total of 228 individuals had subclinical renal disease by 2017. Compared with the low stable trajectory group, the other groups had increasingly greater odds of experiencing subclinical renal disease in middle age. These associations were not altered after adjustment for other covariates, except for in the moderate stable group. Analyzed results were similar for the mean arterial pressure and diastolic BP trajectory groups.ConclusionsHigher BP trajectories were correlated with higher of uACR levels and risk of subclinical renal disease in middle age. Identifying long-term BP trajectories from early age may assist in predicting individuals’ renal function in later life.

A time-course study of gene expression and antibody repertoire at early time post vaccination of Atlantic salmon

2019 ◽  
Vol 106 ◽  
pp. 99-107 ◽  
Author(s):  
Hege Lund ◽  
Anne Flore Bakke ◽  
Ingunn Sommerset ◽  
Sergey Afanasyev ◽  
Geir Schriwer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atlantic Salmon ◽  
Time Course ◽  
Early Time ◽  
Antibody Repertoire ◽  
Post Vaccination ◽  
Time Course Study

Thrombus organization and healing in the swine experimental aneurysm model. Part I. A histological and molecular analysis

2007 ◽  
Vol 107 (1) ◽  
pp. 94-108 ◽  
Author(s):  
Daniel Lee ◽  
Ichiro Yuki ◽  
Yuichi Murayama ◽  
Alexander Chiang ◽  
Ichiro Nishimura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Analysis ◽  
Time Course ◽  
Collagen Deposition ◽  
Expression Analysis Systematic Explorer ◽  
Experimental Aneurysm ◽  
Tissue Organization ◽  
Time Course Study ◽  
Immunohistochemical Studies ◽  
Aneurysm Model

Object The authors describe the process of thrombus organization in the swine surgical aneurysm model. Methods Lateral carotid artery aneurysms with immediately induced thrombosis were created in 31 swine for a time-course study. Aneurysms were evaluated at 1, 3, 7, 14, 30, and 90 days after they were created. Histological analyses included quantitative immunohistochemical studies and evaluation of collagen deposition. Complementary DNA microarray analysis was performed for gene expression profiling. The lists of up- and downregulated genes were cross-matched with lists of genes known to be associated with cytokines or the extracellular matrix. The expression of selected genes was quantified using real-time polymerase chain reaction. Functional clustering was performed with the Expression Analysis Systematic Explorer (EASE) bioinformatics package. Results Histological analysis demonstrated leukocyte and macrophage infiltration in the thrombus at Day 3, myofibroblast infiltration at Days 7 to 14, and progressive collagen deposition and contraction thereafter. Tissue organization occurred in a centripetal fashion. A previously undescribed reticular network of connective tissue was observed at the periphery of the aneurysm at Day 3. Macrophages appeared critical to this thrombus organization. A total of 1109 genes were significantly changed from reference time zero during the time course: CXCL14, which produces a monocyte-specific chemokine, was upregulated over 100-fold throughout the time course; IGF1 was upregulated fourfold at Day 7, whereas IGFBP2 was downregulated approximately 50% at Days 7 and 14. Osteopontin (SPP1) upregulation increased from 30-fold at Day 30 to 45-fold at Day 14. The EASE analysis yielded eight functional classes of gene expression. Conclusions This investigation provides a detailed histological and molecular analysis of thrombus organization in the swine aneurysm model. The companion study will describe the effect of embolic bioabsorbable polymers on this process.

scholarly journals Profiling of zinc-altered gene expression in human prostate normal vs. cancer cells: a time course study

2009 ◽  
Vol 20 (12) ◽  
pp. 1000-1012 ◽  
Author(s):  
Shu-fei Lin ◽  
Hua Wei ◽  
Dennis Maeder ◽  
Renty B. Franklin ◽  
Pei Feng
Keyword(s):  
Gene Expression ◽  
Cancer Cells ◽  
Time Course ◽  
Human Prostate ◽  
Altered Gene Expression ◽  
Time Course Study ◽  
Altered Gene

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 Effect of Fasting on c-Fos Expression in the Hypothalamic Nuclei and Nucleus of the Solitary Tract in Male Rats: Time Course Study and the Role of Testosterone.

2001 ◽  
Vol 47 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Beverly A. S. REYES ◽  
Sakiko YAMADA ◽  
Maria Amelita C. ESTACIO ◽  
Kei-Ichiro MAEDA ◽  
Hiroko TSUKAMURA
Keyword(s):  
Time Course ◽  
Male Rats ◽  
Solitary Tract ◽  
Hypothalamic Nuclei ◽  
Fos Expression ◽  
Time Course Study

scholarly journals The transcription factor reservoir and chromatin landscape in activated plasmacytoid dendritic cells

2021 ◽  
Author(s):  
Ritu Mann-Nüttel ◽  
Shafaqat Ali ◽  
Patrick Petzsch ◽  
Karl Köhrer ◽  
Judith Alferink ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dendritic Cells ◽  
Time Course ◽  
Target Genes ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Type I ◽  
A Cell ◽  
Direct Binding ◽  
Time Course Study

Transcription factors (TFs) control gene expression by direct binding to regulatory regions of target genes but also by impacting chromatin landscapes and thereby modulating DNA accessibility for other TFs. To date, the global TF reservoir in plasmacytoid dendritic cells (pDCs), a cell type with the unique capacity to produce unmatched amounts of type I interferons, has not been fully characterized. To fill this gap, we have performed a comprehensive analysis in naïve and TLR9-activated pDCs in a time course study covering early timepoints after stimulation (2h, 6h, 12h) integrating gene expression (RNA-Seq), chromatin landscape (ATAC-Seq) and Gene Ontology studies. We found that 70% of all described TFs are expressed in pDCs for at least one stimulation time point and that activation predominantly "turned on" the chromatin regions associated with TF genes. We hereby define the complete set of TLR9-regulated TFs in pDCs. Further, this study identifies the AP-1 family of TFs as potentially important but so far less well characterized regulators of pDC function.

scholarly journals Nephroprotective effect of silymarin against diclofenac induced renal damage and oxidative stress in male rats

2019 ◽  
Vol 8 (2) ◽  
pp. 146-152 ◽  
Author(s):  
Ali Nouri ◽  
Esfandiar Heidarian
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Vitamin C ◽  
Group Treatment ◽  
Renal Damage ◽  
Male Rats ◽  
Tissue Homogenate ◽  
Control Group ◽  
Tnf Α ◽  
And Oxidative Stress

Introduction: Diclofenac (DIC), a phenylacetic acid compound which belongs to nonsteroidal anti-inflammatory drugs (NSAIDs), is generally used for the treatment of various diseases such as rheumatoid arthritis, ankylosing spondylitis, acute muscle pain conditions and osteoarthritis. Overdose of DIC can lead to renal injuries in both experimental animal and human. Our research was done to assess the protective role of silymarin on renal damage induced by DIC in rats. Methods: Thirty-two Wistar rats were assigned to four groups (n=8/group). Group 1 was control group; animals in group 2 were administrated DIC; Groups 3 and 4 administrated DIC plus silymarin with doses of 100 mg/kg and 200 mg/kg, orally (p.o), respectively. Various biochemical, molecular, and histological parameters were evaluated in serum and tissue homogenate. Results: In the second group, the levels of kidney catalase (CAT), vitamin C and superoxide dismutase (SOD) remarkably reduced (P < 0.05) relative to the control group. Also, urea, creatinine (Cr), malondialdehyde (MDA), serum tumor necrosis factor-α (TNF-α) and gene expression of TNF-α in this group were noticeably elevated (P < 0.05) relative to the control group. Treatment with silymarin caused a remarkable elevation (P < 0.05) in vitamin C, SOD, CAT and a remarkable reduction (P < 0.05) in the content of MDA, urea, Cr, TNF-α gene expression and serum TNF-α in comparison with second group. Histological injuries were also ameliorated by silymarin administration. Conclusion: The results confirm that silymarin has an ameliorative role against renal damage and oxidative stress induced by DIC in male rats.

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