Deletion of all microRNAs (miRNAs) in nephron progenitors leads to premature loss these cells, but the roles specific miRNAs have not been identified. Deletions MIR17HG cluster (miR-17~92 mice), detected a subset patients with Feingold syndrome, represent first miRNA mutations be associated developmental defect humans. Although is expressed developing kidney, and syndrome caused by MYCN renal anomalies, it remains unclear what extent contributes development function. To define role...

A role for microRNAs (miRs) in the physiologic regulation of sodium transport kidney has not been established. In this study, we investigated potential aldosterone to alter miR expression mouse cortical collecting duct (mCCD) epithelial cells. Microarray studies demonstrated by both cultured mCCD and isolated primary distal nephron principal Aldosterone most significantly downregulated miRs, mmu-miR-335–3p, mmu-miR-290–5p, mmu-miR-1983 was confirmed quantitative RT-PCR. Reducing these miRs...

MicroRNAs (miRNAs) are small, noncoding regulatory RNAs that act as posttranscriptional repressors by binding to the 3'-untranslated region (3'-UTR) of target genes. They require processing Dicer, an RNase III enzyme, become mature RNAs. Previous work from our laboratory revealed critical roles for miRNAs in nephron progenitors at midgestation (Ho J, Pandey P, Schatton T, Sims-Lucas S, Khalid M, Frank MH, Hartwig Kreidberg JA. J Am Soc Nephrol 22: 1053-1063, 2011). To interrogate early...

MicroRNAs are small noncoding RNAs that post-transcriptionally regulate mRNA levels. While previous studies have demonstrated miRNAs indispensable in the nephron progenitor and ureteric bud lineage, little is understood about stromal during kidney development. The renal stroma (marked by expression of FoxD1) gives rise to interstitium, a subset peritubular capillaries, multiple supportive vascular cell types including pericytes glomerular mesangium. In this study, we generated...

Significance Statement Regulation of endothelial cells is important in many biologic processes, including development, organ function, and disease. The kidney vasculature highly sensitive to hypoxic injury has a limited capacity for repair. AKI as result decreased blood flow common, there are no current therapies. MicroRNAs small noncoding RNAs that inhibit expression target genes. Endothelial-derived miR-17∼92 cluster microRNAs critical function repair during mice. Furthermore,...

The epithelial sodium channel (ENaC) is expressed in the cells of distal convoluted tubules, connecting and cortical collecting duct (CCD) kidney nephron. Under regulation steroid hormone aldosterone, ENaC a major determinant (Na+ ) water balance. ability aldosterone to regulate microRNAs (miRs) has recently been realized, but role miRs Na+ not well established. Here we demonstrate that expression miR cluster mmu-miR-23-24-27, upregulated CCD by stimulation both vitro vivo. Increasing these...

Nephron progenitors, the cell population that give rise to functional unit of kidney, are metabolically active and self-renew under glycolytic conditions. A switch from glycolysis mitochondrial respiration drives these cells toward differentiation, but mechanisms control this poorly defined. Studies have demonstrated kidney formation is highly dependent on oxygen concentration, which largely regulated by von Hippel-Lindau (VHL; a protein component ubiquitin ligase complex) hypoxia-inducible...

The final steps in the Renin-Angiotensin-Aldosterone signaling System (RAAS) involve binding of corticosteroid hormone, aldosterone to its mineralocorticoid receptor (MR). bound MR interacts with response elements induce or repress transcription aldosterone-regulated genes. A well characterized aldosterone-induced gene is serum and glucocorticoid-induced kinase (SGK1), which acts downstream increase sodium transport distal kidney nephron epithelial cells. role microRNAs (miRs) induced by...

Low nephron endowment at birth has been associated with an increased risk for developing hypertension and chronic kidney disease. We demonstrated in earlier study that conditional deletion of the microRNA (miRNA)-processing enzyme Dicer from progenitors results premature depletion expression proapoptotic protein Bim (also known as Bcl-2L11). In this study, we generated a compound mouse model both Bim, to determine biologic significance Dicer-deficient progenitors. The loss partially restored...

We have previously demonstrated that loss of miR-17~92 in nephron progenitors a mouse model results renal hypodysplasia and chronic kidney disease. Clinically, decreased congenital endowment because is associated with an increased risk hypertension disease, this at least partly dependent on the self-renewal progenitors. Here, we present evidence for novel molecular mechanism regulating by highly conserved cluster. Whole transcriptome sequencing revealed lacking cluster Cftr expression....

The incidence of diabetes mellitus has significantly increased among women childbearing age, and it been shown that prenatal exposure to maternal increases the risk associated congenital anomalies kidney. Congenital kidney are leading causes chronic disease in children. To better understand effect on development, we analyzed wild-type offspring (DM_Exp) diabetic

Low nephron number results in an increased risk of developing hypertension and chronic kidney disease. Intrauterine growth restriction is associated with a deficit humans, commonly caused by placental insufficiency, which fetal hypoxia. The underlying mechanisms hypoxia impacts development are poorly understood. microRNA-210 the most consistently induced microRNA known to promote cell survival hypoxic environment. In this study, role was evaluated using global knockout mouse. A male-specific...

A catheter coating consisting of polydimethylsiloxane (PDMS) mixed with powdered metals silver and zinc has been investigated. The is easily applicable to existing silicone devices effective in inhibiting the formation biofilm. Following manufacturing coating, its surface materials characteristics were analyzed through scanning electron microscopy (SEM) energy dispersive X-ray (EDX). antibacterial properties investigated by applying a thin film standard catheter. unique formulation was found...

Abstract The kidney is a complex organ composed of more than 30 terminally differentiated cell types that all are required to perform its numerous homeostatic functions. Defects in development significant cause chronic disease children, which can lead failure only be treated by transplant or dialysis. A better understanding molecular mechanisms drive important for designing strategies enhance renal repair and regeneration. In this study, we profiled gene expression the developing mouse at...

Mammalian nephrons originate from a population of nephron progenitor cells, and changes in these cells' transcriptomes contribute to the cessation nephrogenesis, an important determinant number. To characterize microRNA (miRNA) expression identify putative cis-regulatory regions, we collected cells mouse kidneys at embryonic day 14.5 postnatal zero assayed small RNA transposase-accessible chromatin. We detect 1104 miRNA (114 with changes), 46,374 chromatin accessible regions (2103...

Expression of the microRNA-17-92 cluster is upregulated by aldosterone in mouse cortical collecting duct principal cells, exclusively female mice. MiR-19 this targets serum and glucocorticoid kinase (SGK1) to downregulate both mRNA protein expression, resulting a decrease sodium transport across epithelial cells duct. The miR-17-92 evolutionarily conserved may act as novel feedback regulator for signaling females.

Background: Hypertension affects more than one billion people worldwide. A key regulator of blood pressure homeostasis is aldosterone, the final signaling hormone renin-angiotensin-aldosterone-signaling (RAAS) system. Aldosterone increases sodium (Na+) transport in kidney distal nephron to regulate volume. We previously demonstrated that aldosterone alters expression microRNAs (miRs) collecting duct epithelial cells modulate Na+ response aldosterone. In this study a novel miR cluster,...

Abstract The clinical efficacy of the anticancer agent etoposide (VP-16) is compromised by its ability to cause acute myeloid leukemias (t-AML) associated with MLL gene rearrangements. We proposed previously that myeloperoxidase (MPO) found in precursors converts phenolic drug VP-16 phenoxyl radical (VP-16-O[[Unable Display Character: ∙]]), which redox cycles, leading generation reactive oxygen species, oxidative DNA damage linked topoisomerase II (topo II)-mediated strand...

Regulated sodium (Na + ) homeostasis in the kidney is achieved by action of renin‐angiotensin‐aldosterone signaling cascade. The terminal hormone, aldosterone binds to mineralocorticoid receptor (MR) increase Na uptake across tubule epithelial cells altering expression and function channels, transporters regulatory proteins acting concert. Along with a change gene protein expression, regulates non‐coding RNAs including microRNAs (miRs). primary miRs repress target mRNA decrease abundance....