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Whole Transcriptome Analysis of Renal Intercalated Cells Predicts Lipopolysaccharide Mediated Inhibition of Retinoid X Receptor alpha Function.

ABSTRACT: The renal collecting duct consists of intercalated cells (ICs) and principal cells (PCs). We have previously demonstrated that collecting ducts have a role in the innate immune defense of the kidney. Transcriptomics is an important tool used to enhance systems-level understanding of cell biology. However, transcriptomics performed on whole kidneys provides limited insight of collecting duct cell gene expression, because these cells comprise a small fraction of total kidney cells. Recently we generated reporter mouse models to enrich collecting duct specific PC and ICs and reported targeted gene expression of anti-microbial peptide genes. Here we report transcriptomics on enriched ICs and PCs and performed a pilot study sequencing four single ICs. We identified 3,645 genes with increased relative expression in ICs compared to non-ICs. In comparison to non-PCs, 2,088 genes had higher relative expression in PCs. IC associated genes included the innate interleukin 1 receptor, type 1 and the antimicrobial peptide(AMP) adrenomedullin. The top predicted canonical pathway for enriched ICs was lipopolysaccharide/Interleukin 1 mediated inhibition of Retinoid X Receptor alpha function and decreased Retinoid X Receptor expression was confirmed to occur 1-hour post experimental murine UTI in ICs but not in non-ICs.

SUBMITTER: Saxena V

PROVIDER: S-EPMC6345901 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Whole Transcriptome Analysis of Renal Intercalated Cells Predicts Lipopolysaccharide Mediated Inhibition of Retinoid X Receptor alpha Function.

Saxena Vijay V Fitch James J Ketz John J White Peter P Wetzel Amy A Chanley Melinda A MA Spencer John D JD Becknell Brian B Pierce Keith R KR Arregui Sam W SW Nelson Raoul D RD Schwartz George J GJ Velazquez Victoria V Walker Logan A LA Chen Xi X Yan Pearlly P Hains David S DS Schwaderer Andrew L AL

Scientific reports 20190124 1

The renal collecting duct consists of intercalated cells (ICs) and principal cells (PCs). We have previously demonstrated that collecting ducts have a role in the innate immune defense of the kidney. Transcriptomics is an important tool used to enhance systems-level understanding of cell biology. However, transcriptomics performed on whole kidneys provides limited insight of collecting duct cell gene expression, because these cells comprise a small fraction of total kidney cells. Recently we gen ...[more]

PMID: 30679625

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Project description:The purpose of this study was to define the relationship between left ventricular diastolic function and survival after renal revascularization.Seventy-six adult patients (49 women, 27 men; mean age: 63 ± 13 years) with preoperative echocardiography who underwent renal revascularization for atherosclerotic disease were identified. Diastolic function was estimated from the early diastolic transmitral flow velocity (E), the atrial transmitral flow velocity (A), and the mitral annular tissue doppler velocity (e'). Patients were divided into two groups of diastolic dysfunction as either none/mild (E/A ? 0.75, E/e' <10) or moderate/severe (E/A >0.75, E/e' ? 10). Perioperative and follow-up mortality were determined from a prospective vascular database and the National Death Index. Descriptive statistics were calculated and postoperative survival was estimated by product-limit methods. Associations between preoperative factors, perioperative factors, and follow-up survival were examined using proportional hazards regression models. A forward stepwise variable selection procedure was used to select a "best" model to predict follow-up survival.Seventy-six patients were followed for an average of 41.9 months after renal revascularization. Within this group, 47 of 76 patients (61.8%) were identified as having moderate or severe diastolic dysfunction. Diastolic dysfunction had no apparent association with abnormal systolic function. The mean ejection fraction for those with moderate/severe diastolic dysfunction was 57.7% ± 11.5%. When comparing the moderate/severe and none/mild groupings of diastolic dysfunction, there was a significant difference in left ventricular mass index (151.9 ± 48.9 vs 125.3 ± 31.7; P = .0087). There were five deaths in the perioperative period and 20 deaths on follow-up. Among perioperative survivors, hypertension was cured or improved in 82% of the none/mild group and 53% of the moderate/severe group (P = .012). In multivariable analysis, none/mild diastolic dysfunction was significantly and independently associated with an improvement in blood pressure after revascularization (odds ratio [OR], 6.2; 95% confidence interval [CI], 1.4-28.6; P = .018). Ejection fraction was not associated with survival. After forward variable selection, moderate/severe diastolic dysfunction (hazard ratio [HR], 5.8; 95% CI 1.4-25; P = .018) was the only variable to demonstrate a significant and independent association with follow-up survival.Diastolic dysfunction, but not systolic dysfunction, was frequent in patients with renovascular disease. Blood pressure response and follow-up survival after renal revascularization demonstrated significant and independent associations with diastolic function. Consideration of diastolic function should be included in the management of patients with atherosclerotic renovascular disease.

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Whole Transcriptome Analysis of Renal Intercalated Cells Predicts Lipopolysaccharide Mediated Inhibition of Retinoid X Receptor alpha Function.

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Whole Transcriptome Analysis of Renal Intercalated Cells Predicts Lipopolysaccharide Mediated Inhibition of Retinoid X Receptor alpha Function.

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