Insulin receptor deletion in kidney intercalated cells suppresses collecting duct immune defenses
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ABSTRACT:
PROVIDER: PRJNA883415 | ENA |
REPOSITORIES: ENA
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Project description:Urinary tract infection (UTI) significantly impacts people with diabetes mellitus. Insulin resistance, the primary abnormality leading to Type 2 diabetes, is defined by inefficient insulin receptor signaling. In the kidney, insulin receptor deletion in intercalated cells increases UTI susceptibility. Here, we use RNA sequencing to profile the transcriptomes of enriched intercalated cell and neighboring principal cell populations from mice with intercalated cell-specific insulin receptor deletion and compare expression profiles to wild-type mice. We also establish unique intercalated cell and principal cell cultures to assess the functional impact of insulin receptor deletion. Transcriptomic analysis and culture models demonstrate intercalated cells with insulin receptor deletion are more susceptible to uropathogenic Escherichia coli infection and have suppressed integrated stress responses. They also show the integrated stress response is necessary to activate NFkB-mediated immune responses. When NFkB is silenced, intercalated cells do not activate innate immune responses, including the production of antimicrobial peptides, which increases infection susceptibility.
2024-07-08 | GSE213985 | GEO
Project description:Analysis of collecting duct response to low NaCl or high NaCl diet at the gene expression level. Results provide insight into transcriptional changes in principal and intercalated cells that occur in response to changes in dietary NaCl.
2018-11-28 | GSE122995 | GEO
Project description:People with diabetes mellitus have increased infection risk. With diabetes, urinary tract infection (UTI) is more common and has worse outcomes. Here, we investigate how diabetes and insulin resistance impact the kidney's innate defenses and urine sterility. We report that type 2 diabetic mice have increased UTI risk. Moreover, insulin-resistant prediabetic mice have increased UTI susceptibility, independent of hyperglycemia or glucosuria. To identify how insulin resistance affects renal antimicrobial defenses, we genetically deleted the insulin receptor in the kidney's collecting tubules and intercalated cells. Intercalated cells, located within collecting tubules, contribute to epithelial defenses by acidifying the urine and secreting antimicrobial peptides (AMPs) into the urinary stream. Collecting duct and intercalated cell-specific insulin receptor deletion did not impact urine acidification, suppressed downstream insulin-mediated targets and AMP expression, and increased UTI susceptibility. Specifically, insulin receptor-mediated signaling regulates AMPs, including lipocalin 2 and ribonuclease 4, via phosphatidylinositol-3-kinase signaling. These data suggest that insulin signaling plays a critical role in renal antibacterial defenses.
| S-EPMC6264632 | biostudies-literature
Project description:Purpose: Transport processes in the renal collecting duct are responsible for precise regulation of blood pressure and body fluid composition. The collecting duct is composed of at least three cell types, type A intercalated cells (A-IC), type B intercalated cells (B-IC) and principal cells (PC). To identify the genes that are selectively expressed in each cell type, including cell-surface receptors, transcription factors, transporters and secreted proteins, we used cell surface markers necessary for isolation of each of the three cell types using fluorescence-activated cell sorting and carried out single-cell RNA-Seq to measure the mRNA species in each of these cell types. Methods: We enriched each of the three cell types using fluorescence-activated cell sorting. Subsequently, we carried out single-cell RNA-Seq of those cells using a microfluidic chip (Fluidigm C1 system). Single-cell cDNA libraries were constructed for paired-end sequencing and sequenced on Illumina HiSeq3000 platform. In addition, we also microdissected mouse CCDs and cTALs and carried out single-tubule RNA-Seq. Reads were mapped to mouse Ensembl Genome by STAR and transcript abundances were calculated in the units of transcripts per million (TPM) using RSEM (https://github.com/deweylab/RSEM). Single-cell RNA-Seq data anaysis were carried out using Seurat package in R. Results and conclusion: Single-cell cDNA libraries were constructed for paired-end sequencing and at least 10-million sequence reads per cell were mapped to the mouse genome (Ensembl, GRCm38.p5). On average, cells were sequenced to a depth of 3000 genes (TPM>1). Unsupervised clustering analysis revealed five different cell types, namely type A intercalated cells (n=87), type B intercalated cells (n=23), principal cells (74), proximal tubule cells (n=19), and non-epithelial cells (n=32). The identified patterns of gene expression among A-ICs, B-ICs and PCs provide a foundation for understanding physiological regulation and pathophysiology in the renal collecting duct.
2017-10-31 | GSE99701 | GEO
Project description:Here, establishing expansion cultures of hiPSC-derived ureteric bud tip cells, an embryonic precursor that gives rise to collecting ducts, we succeeded in advancing the developmental stage of collecting duct organoids and showed that all collecting duct organoids derived from PKD1-/- hiPSCs spontaneously develop multiple cysts, clarifying the initiation mechanisms of cystogenesis.
2023-11-30 | GSE215875 | GEO
Project description:Analysis of expression changes in renal collecting duct epithelial cells by adenoviral mediated Krüppel like transcription factor 5 (KLF5) overexpression. KLF5 is a key regulator of static and inflammatory stage in renal collecting duct epithelial cells. We thought these results provide insights into downstream genes of KLF5 in renal collecting duct epithelial cells.
2011-05-17 | GSE29323 | GEO
Project description:Identification of gene expressed in the enriched inner medullary collecting duct cells in rat. Experiment Overall Design: Rat inner medullary collecting duct (IMCD) cells were isolated from 7 male Sprage-Dawley rats by collagenase and hyaluronidase digestion and follow by low speed centrifugation. The non-IMCD cells were collected by centrifugation of supernatant of enriched IMCD samples. Experiment Overall Design: Total RNA about 3 ug were used per microarray (Rat 230 2.0 Genechip array). Experiment Overall Design: The experiments were repeat 3 times (3 pairs of IMCD VS non-IMCD)
2008-06-15 | E-GEOD-7891 | biostudies-arrayexpress
Project description:Identification of gene expressed in the enriched inner medullary collecting duct cells in rat. Keywords: gene expression comparision between cell type
2007-12-21 | GSE7891 | GEO
Project description:Transcriptional profiling of new born mouse kidney collecting duct (CD) cells comparing the infuence of gestational high salt stress on gene expression remolding of BdkrB2 receptor knockout CD cells with that of BdkrB2 receptor wild type CD cells. The BdkrB2 receptor has been shown to be playing a role in renal vascular tone, kidney secretion and reabsorption function, normal kidney development, while impaired BdkrB2 receptor in kidney shown being associated with renal agenesis and renal dysplasia. Goal was to determine the effects of BdkrB2 receptor knockout together with gestational high salt stress on collecting duct gene expression pattern.
2013-08-08 | GSE49616 | GEO
Project description:Analysis of expression changes in renal collecting duct epithelial cells by adenoviral mediated Krüppel like transcription factor 5 (KLF5) overexpression. KLF5 is a key regulator of static and inflammatory stage in renal collecting duct epithelial cells. We thought these results provide insights into downstream genes of KLF5 in renal collecting duct epithelial cells. Total RNAs were isolated from adenovirally-mediated KLF5 over expressed cultured mIMCD-3 cells or control adenovirus infected mIMCD-3. We analyzed these two gene expression profiles after 24 hours after infection.
2011-05-17 | E-GEOD-29323 | biostudies-arrayexpress