Single nucleus transcriptomics to study sex differences during murine E. coli pyelonephritis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE296327 | GEO | 2026/02/18
REPOSITORIES: GEO
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Project description:Urinary tract infections are common and often recur. Using a pyelonephritis mouse model, we investigated the interplay between renal and systemic inflammation. Bulk RNA sequencing analysis of kidneys collected 16 hours post-infection was performed to identify novel regulators and modulators of inflammatory pathways. Our results highlight key molecular signatures involved in both local and systemic immune responses, providing new insights into the regulatory networks underlying the pathophysiology of pyelonephritis.
2026-02-27 | GSE308447 | GEO
Project description:Renal scarring is a serious complication of chronic pyelonephritis due to vesicoureteral reflux, and requires specific biomarker for indication of early intervention. We investigated global expression profile of kidney during renal scarring formation using rat pyelonephritis model. An inoculum of the DS-17 strain Escherchia coli was injected directly into renal cortex of Wister rat. Histologically, renal scarring developed during 3 and 4 weeks after injection. The time course expression profile of approximately 20,500 genes was analyzed using high density oligonucleotide microarray followed by validation using real time RT-PCR. Most of up-regulated genes during this experimental renal scarring were associated with immune and defense response, including cytokines, chemokines, their receptors, complements, and adhesion molecules as well as proteins related to extra cellular matrix. These genes were up-regulated as early as 1 week after injection when histological examination did not show fibrotic change yet, peaked at 2 weeks and gradually decreased thereafter. However, a subset of cytokine genes is persistently activated even in 6 weeks after the injection, which are involved in TGF-β related tissue regeneration pathway or IL-1β related pathway. The products of these genes may potentially be the source of novel non-invasive diagnostic or prognostic biomarkers for renal scarring. Experiment Overall Design: Experimental pyelonephritis was produced by standard method of direct infection of rat kidney. In brief, animals were anesthetized with pentobarbital intraperitoneally. The kidneys were exposed through a midline abdominal incision. An inoculum of 1x109 colony-forming units / 0.1 ml of Escherchia coli was injected directly into bilateral renal cortex of Wister rat using 26-gauge needle. We used DS-17 or NU-14 strains, both of which has type 1 and P pili, and SEC strain, which has only type 1 pili. Control rats received isotonic saline instead of bacterial solution. Both test and control kidneys were harvested at 1, 2, 4 and 6 weeks after injection. The kidney samples (1x1x2 mm each) were obtained including the injection site, which was easily identified by surface color change. Then we cut the kidney into half; one was used for microscopic examination and the other half was immediately frozen in liquid nitrogen for later RNA extraction.
2008-06-15 | E-GEOD-7087 | biostudies-arrayexpress
Project description:Despite a growing body of knowledge regarding the pathogenesis of urinary tract infection, the mechanisms of renal scaring associated with acute pyelonephritis (APN) are poorly understood. Limited data available regarding histopathology, immune cell recruitment and gene expression changes during APN severely restricts the development of therapies to prevent renal scars. Here, we address this knowledge gap using inbred, immunocompetent mice with vesicoureteral reflux. Transurethral inoculation of uropathogenic Escherichia coli leads to renal mucosal injury, tubulointerstitial nephritis, and interstitial fibrosis – all histopathologic features of human APN. Interstitial fibrosis correlates most significantly with inflammation 7 and 28 days post infection. Flow cytometry identifies recruitment of neutrophils, macrophages, and lymphocytes to infected kidneys. Renal transcriptional analysis reveals molecular signatures associated with renal ischemia-reperfusion injury, immune cell chemotaxis, and leukocyte activation. Thus, C3H/HeOuJ mice with APN comprise a novel model of renal fibrosis that recapitulates the human condition of acquired renal scarring in an immunocompetent setting. The integration of organ pathology, quantitative cellular immune influx, and transcriptional analyses begin, for the first time, to define mechanisms of tissue injury during APN in the context of an intact immune response. The strong relationship between pro-inflammatory cell recruitment and fibrosis supports the hypothesis that renal scarring arises as a consequence of excessive host inflammation. Our studies suggest that immunomodulatory therapies should be investigated to reduce renal scarring in patients with APN.
2016-12-29 | GSE76469 | GEO
Project description:Renal scarring is a serious complication of chronic pyelonephritis due to vesicoureteral reflux, and requires specific biomarker for indication of early intervention. We investigated global expression profile of kidney during renal scarring formation using rat pyelonephritis model. An inoculum of the DS-17 strain Escherchia coli was injected directly into renal cortex of Wister rat. Histologically, renal scarring developed during 3 and 4 weeks after injection. The time course expression profile of approximately 20,500 genes was analyzed using high density oligonucleotide microarray followed by validation using real time RT-PCR. Most of up-regulated genes during this experimental renal scarring were associated with immune and defense response, including cytokines, chemokines, their receptors, complements, and adhesion molecules as well as proteins related to extra cellular matrix. These genes were up-regulated as early as 1 week after injection when histological examination did not show fibrotic change yet, peaked at 2 weeks and gradually decreased thereafter. However, a subset of cytokine genes is persistently activated even in 6 weeks after the injection, which are involved in TGF-β related tissue regeneration pathway or IL-1β related pathway. The products of these genes may potentially be the source of novel non-invasive diagnostic or prognostic biomarkers for renal scarring. Keywords: renal scarring, TGF-β , IL-1β
2007-02-22 | GSE7087 | GEO
Project description:Urinary tract infections (UTI) are frequent and highly inflammatory. Using a pyelonephritis mouse model, we investigated the impact of pyelonephritis on the development of atherosclerosis. Bulk RNA sequencing analysis of kidneys and aortas harvested four weeks post-infection was performed to identify key molecular markers and delineate differentially regulated inflammatory pathways in both organs. Our results show an upregulation of inflammatory mediators in kidney and aorta, providing a possible mechanistic link between pyelonephritis and atherosclerosis.
2026-04-04 | GSE313813 | GEO
Project description:Antimicrobial peptides (AMPs) serve key proposed roles in defending the urinary tract against invading uropathogens, but individual AMPs bearing greatest responsibility for these functions remain largely unknown. We identified RegIIIγ as the most transcriptionally upregulated AMP in bladder transcriptomes following uropathogenic Escherichia coli (UPEC) infection. We confirmed induction of RegIIIγ mRNA during cystitis and pyelonephritis by quantitative RT-PCR. Immunoblotting demonstrates increased bladder and urinary RegIIIγ protein levels following UPEC infection. Immunostaining localizes RegIIIγ protein to urothelial cells of infected bladders and kidneys. Human patients with cystitis and pyelonephritis exhibit increased urine levels of the orthologous HIP/PAP protein. Recombinant RegIIIγ protein does not demonstrate bactericidal activity toward UPEC in vitro, but does kill Staphylococcus saprophyticus in a dose-dependent manner. RegIIIγ knockout and control urinary tracts contain comparable bacterial burden following experimental inoculation of UPEC as well as Gram-positive uropathogens. Thus, while RegIIIγ and HIP/PAP expression occurs in human and murine UTI, their specific functions in the urinary tract remain uncertain.
2015-12-29 | GSE72007 | GEO
Project description:Vesicoureteral reflux (VUR) is a common pediatric condition that predisposes children to renal damage after urinary tract infection (UTI). We profiled the urinary proteome of VUR patients with recurrent UTI and renal scarring to identify potential biomarkers characterizing this condition. Urine was obtained from 22 age-matched controls and 22 patients with low grade VUR (1-3 out of 5), renal scarring, and history of recurrent UTI. Proteins extracted from these samples were analyzed by mass spectrometry for protein identification and quantitation for comparison.
2018-10-05 | PXD010469 | Pride
Project description:Obesity is a significant public health concern associated with increased infection risk, but the mechanisms remain unclear. Using a diet induced obesity mouse model, we investigate how obesity impacts urinary tract infection (UTI) susceptibility and bladder urothelial defenses. High fat diet-fed female and male C57BL/6 mice exhibit increased susceptibility to uropathogenic E. coli (UPEC) following experimental UTI. Transcriptomic analysis of bladder urothelial cells reveals sex-specific gene expression changes, but both sexes share activation of focal adhesion and extracellular matrix signaling. Western blot and immunostaining confirm activation of focal adhesion kinase (FAK), a central component of the focal adhesion pathway, in the bladders of obese female and male mice. Mechanistically, primary human urothelial cells overexpressing FAK exhibit increased UPEC invasion. These findings demonstrate that obesity enhances UTI susceptibility and identify FAK as a conserved pathway disrupted by obesity, contributing to increased UPEC vulnerability.
2025-09-19 | GSE294660 | GEO
Project description:Preterm birth is the leading cause of infant mortality resulting in over one million neonatal deaths annually. Maternal urinary tract infection (UTI) during pregnancy increases risk for preterm birth; however, biological processes mediating UTI-associated preterm birth are not well-described. We established a murine maternal UTI model in which challenge with uropathogenic E. coli resulted in preterm birth in about half of dams. Dams experiencing preterm birth displayed excessive bladder inflammation and altered uteroplacental T cell polarization compared to non-laboring infected dams, with no differences in bacterial burdens. Additional factors associated with preterm birth included higher proportions of male fetuses and lower maternal serum IL-10. Furthermore, exogenous maternal IL-10 treatment absolved UTI-associated preterm birth but contributed to fetal growth restriction in this model.
2025-10-23 | GSE280297 | GEO
Project description:Urinary tract infections (UTI) stand as one of the most prevalent infections worldwide. Uropathogenic Escherichia coli (UPEC) is the primary cause of UTI, instigating 75% of uncomplicated and 65% of complicated UTIs. Innate immune cells play pivotal roles in eliminating invading uropathogens and represent a potential therapeutic target for UTI prevention and treatment. Previous studies in our laboratory demonstrated that selective depletion of neutrophils during experimental UTI, results in an uncontrolled infection and augmented bladder and kidney pathologies. However, the exact antimicrobial mechanisms employed by neutrophils to eliminate multi-drug resistant uropathogens, such as UPEC, and resolve UTI remain poorly understood. Our dataset provides insight of the multifaceted role of neutrophil NOX2 in UPEC elimination and regulation of inflammatory and effector functions of these innate immune cells. Our transcriptome analyses revealed a heightened pro-inflammatory profile in NOX2-deficient neutrophils compared to WT neutrophils after UPEC stimulation.
2025-02-28 | GSE256399 | GEO