Pyelonephritis decreases serum cholesterol and mitigates atherosclerosis severity despite systemic inflammation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE308447 | GEO | 2026/02/27
REPOSITORIES: GEO
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Project description:Pyelonephritis decreases serum cholesterol and mitigates atherosclerosis severity despite systemic inflammation
| PRJNA1330608 | ENA
Project description:This project employs models of urinary tract infection (UTI) in female, androgen-exposed female, and male mice to determine molecular mechanisms by which host androgen exposure promotes Escherichia coli pyelonephritis as well as renal scarring, a common sequela of upper-tract UTI. Our prior findings indicated that the influence of sex, including androgen exposure, on these common bacterial infections is more complex than previously appreciated. Specifically, male sex was associated with increased risk for chronic cystitis and high-titer pyelonephritis, as well as formation of renal abscesses. These snRNA-seq experiments were designed to interrogate the fundamental sex differences impacting the host-pathogen interaction and cellular responses in E. coli pyelonephritis, thereby influencing pathogenicity and outcome of infection.
2026-02-18 | GSE296327 | 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:Tertiary lymphoid tissues (TLTs) are formed in systemic organs manifesting chronic inflammation. Herein, we found that the renal pelvis (RP) could form urinary tract-associated lymphoid tissues (UTALTs) in a TLT-formation manner in humans and mice with chronic kidney disease (CKD), regardless of infectious pyelonephritis. Furthermore, collagen type XVII alpha 1 chain (COL17A1), localized ectopically to the transitional epithelium (TE) covering the UTALT, where it participated in TE development via immunological stimulation of UTALT-forming cells.
2022-01-26 | GSE151929 | 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:Mutation of marA, rob, and soxS causes a clinical strain of E.coli to be attenuated at d3 post-infection in a mouse model of pyelonephritis, here we extract RNA at d2 post infection to analyze transcriptional differences between the two strains.
2010-10-01 | GSE23417 | 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:Tertiary lymphoid tissues (TLTs) are formed in systemic organs manifesting chronic inflammation. Herein, we found that the renal pelvis (RP) could form urinary tract-associated lymphoid tissues (UTALTs) in a TLT-formation manner in humans and mice with chronic kidney disease (CKD), regardless of infectious pyelonephritis. Our results demonstrated that urine is crucial for UTALT development. Urine leak from the lumen into the parenchyma of the RP through an altered transitional epithelium (TE) barrier, stimulated RP stromal cells immunologically and attracted immune cells via cytokine and chemokine production. Pathophysiological crosstalk was observed between UTALT development and tubulointerstitial lesions and TLT formation in the kidney.
2022-01-26 | GSE151930 | GEO
Project description:Mutation of marA, rob, and soxS causes a clinical strain of E.coli to be attenuated at d3 post-infection in a mouse model of pyelonephritis, here we extract RNA at d2 post infection to analyze transcriptional differences between the two strains. In order to purify enough bacterial RNA to perform microarray, we chose a time point (day 2 post-infection) just before the triple mutant begins to decrease in bacterial load. Mouse kidneys were extracted, homogonized, and samples were pooled in RNALater (Ambion) before extraction and analysis of the transcriptomes
2010-10-01 | E-GEOD-23417 | biostudies-arrayexpress