David L Mattson

Medical College of Wisconsin, Milwaukee, Wisconsin, United States

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Publications (75)309.64 Total impact

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    Dataset: ROS paper
    Carmen De Miguel · Chuanling Guo · Hayley Lund · Di Feng · David L Mattson

    Full-text · Dataset · Jan 2016
  • Brittany Wade · Justine M Abais-Battad · David L Mattson
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    ABSTRACT: Purpose of review: Immune mechanisms exacerbate the severity of hypertension in humans and animal models of disease. This review summarizes recent mechanistic studies exploring the pathways whereby immunity influences salt-sensitive hypertension and renal disease. Recent findings: Emphasis is placed on the role of T cell subtypes, the mechanisms of T-cell activation, and the identification of potential antigens or neoantigens. Summary: Significant advancements have occurred in the search for pathways which activate the adaptive immune response. An enhanced understanding of the factors contributing to hypertension can lead to better therapies.
    No preview · Article · Nov 2015 · Current Opinion in Nephrology and Hypertension
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    ABSTRACT: The role of immune mechanisms to amplify hypertension in patients and animal models has been appreciated for decades. This review briefly summarizes recent studies exploring the mechanistic pathways, whereby the immune system participates in hypertension and renal disease. Emphasis in this review is placed upon recent studies exploring the role of T cell subtypes, newly described mechanisms of T cell activation, the identification of potential neoantigens, and environmental influences on immune cell activation. Significant advancements have been made in the search for antigens and pathways responsible for activation of the adaptive immune response, furthering our understanding of the factors contributing to hypertension and potentially leading to the development of new and more effective therapies.
    No preview · Article · Jun 2015 · Current Opinion in Nephrology and Hypertension
  • Nathan P Rudemiller · David L Mattson
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    ABSTRACT: Human genetic linkage and association studies have nominated many genes as possible contributors to disease. Mutating or deleting these genes in a relevant disease model can validate their association with disease and potentially uncover novel mechanisms of pathogenesis. Targeted genetic mutagenesis has only recently been developed in the rat, and this technique has been applied in the Dahl salt-sensitive (S) rat to investigate human candidate genes associated with hypertension. This mini-review communicates the findings of these studies and displays how targeted genetic mutagenesis may contribute to the discovery of novel therapies for patients. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    No preview · Article · Apr 2015 · AJP Renal Physiology
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    ABSTRACT: Human genome-wide association studies have linked SH2B adaptor protein 3 (SH2B3, LNK) to hypertension and renal disease, although little experimental investigation has been performed to verify a role for SH2B3 in these pathologies. SH2B3, a member of the SH2B adaptor protein family, is an intracellular adaptor protein that functions as a negative regulator in many signaling pathways, including inflammatory signaling processes. To explore a mechanistic link between SH2B3 and hypertension, we targeted the SH2B3 gene for mutation on the Dahl salt-sensitive (SS) rat genetic background with zinc-finger nucleases. The resulting mutation was a 6-bp, in-frame deletion within a highly conserved region of the Src homology 2 (SH2) domain of SH2B3. This mutation significantly attenuated Dahl SS hypertension and renal disease. Also, infiltration of leukocytes into the kidneys, a key mediator of Dahl SS pathology, was significantly blunted in the Sh2b3(em1Mcwi) mutant rats. To determine whether this was because of differences in immune signaling, bone marrow transplant studies were performed in which Dahl SS and Sh2b3(em1Mcwi) mutants underwent total body irradiation and were then transplanted with Dahl SS or Sh2b3(em1Mcwi) mutant bone marrow. Rats that received Sh2b3(em1Mcwi) mutant bone marrow had a significant reduction in mean arterial pressure and kidney injury when placed on a high salt diet (4% NaCl). These data further support a role for the immune system as a modulator of disease severity in the pathogenesis of hypertension and provide insight into inflammatory mechanisms at play in human hypertension and renal disease. © 2015 American Heart Association, Inc.
    No preview · Article · Mar 2015 · Hypertension
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    ABSTRACT: Research studying the role of inflammation in hypertension and cardiovascular disease has flourished in recent years; however, the exact mechanisms by which the activated immune cells lead to the development and maintenance of hypertension remain to be elucidated. The objectives of this brief review are to summarize and discuss the most recent findings in the field, with special emphasis on potential therapeutics to treat or prevent hypertension. This review will cover novel immune cell subtypes recently associated to the disease including the novel role of cytokines, toll-like receptors, and inflammasomes in hypertension.
    Full-text · Article · Jan 2015 · Current Hypertension Reports
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    ABSTRACT: Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats. © 2014 American Heart Association, Inc.
    No preview · Article · Dec 2014 · Hypertension

  • No preview · Conference Paper · Sep 2014
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    David L Mattson
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    ABSTRACT: The importance of the immune system in hypertension, vascular disease, and renal disease has been appreciated for over 50 years. Recent experimental advances have led to a greater appreciation of the mechanisms whereby inflammation and immunity participate in cardiovascular disease. In addition to the experimental data, multiple studies in patients have demonstrated a strong correlation between the observations made in animals and humans. Of great interest is the development of salt-sensitive hypertension in humans with the concurrent increase in albumin excretion rate. Experiments in our laboratory have demonstrated that feeding a high NaCl diet to Dahl Salt-Sensitive (SS) rats results in a significant infiltration of T-lymphocytes into the kidney that is accompanied by the development of hypertension and renal disease. The development of disease in the Dahl SS closely resembles observations made in patients; studies were therefore performed to investigate the pathological role of infiltrating immune cells in the kidney in hypertension and renal disease. Pharmacological and genetic studies indicate that immune cell infiltration into the kidney amplifies the disease process. Further experiments demonstrated that infiltrating T cells may accentuate the Dahl SS phenotype by increasing intrarenal AngII and oxidative stress. From these and other data, we hypothesize that infiltrating immune cells, which surround the blood vessels and tubules, can serve as a local source of bioactive molecules which mediate vascular constriction, increase tubular sodium reabsorption, and mediate the retention of sodium and water to amplify sodium-sensitive hypertension. Multiple experiments remain to be performed to refine and clarify this hypothesis.
    Preview · Article · Jul 2014 · American journal of physiology. Renal physiology
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    ABSTRACT: Small GTPase Ras-related protein 1 (Rap1b) controls several basic cellular phenomena, and its deletion in mice leads to several cardiovascular defects, including impaired adhesion of blood cells and defective angiogenesis. We found that Rap1b(-/-) mice develop cardiac hypertrophy and hypertension. Therefore, we examined the function of Rap1b in regulation of blood pressure. RAP1B: (-/-) mice developed cardiac hypertrophy and elevated blood pressure, but maintained a normal heart rate. Correcting elevated blood pressure with losartan, an angiotensin II type 1 receptor, alleviated cardiac hypertrophy in Rap1b(-/-) mice, suggesting a possibility that cardiac hypertrophy develops secondary to hypertension. The indices of renal function and plasma renin activity were normal in Rap1b(-/-) mice. Ex vivo, we examined whether the effect of Rap1b deletion on smooth muscle-mediated vessel contraction and endothelium-dependent vessel dilation, 2 major mechanisms controlling basal vascular tone, was the basis for the hypertension. We found increased contractility on stimulation with a thromboxane analog or angiotensin II or phenylephrine along with increased inhibitory phosphorylation of myosin phosphatase under basal conditions consistent with elevated basal tone and the observed hypertension. Cyclic adenosine monophosphate-dependent relaxation in response to Rap1 activator, Epac, was decreased in vessels from Rap1b(-/-) mice. Defective endothelial release of dilatory nitric oxide in response to elevated blood flow leads to hypertension. We found that nitric oxide-dependent vasodilation was significantly inhibited in Rap1b-deficient vessels. This is the first report to indicate that Rap1b in both smooth muscle and endothelium plays a key role in maintaining blood pressure by controlling normal vascular tone.
    Full-text · Article · May 2014 · Arteriosclerosis Thrombosis and Vascular Biology
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    ABSTRACT: Previous studies implicate infiltrating immune cells in the kidney in the pathogenesis of Dahl salt sensitive hypertension. SH2B3, an adaptor protein shown to participate in vascular and inflammatory signaling, is associated with hypertension in human GWAS (Nature Gen 41:667), though the mechanisms underlying the association are unclear. To address this issue, zinc finger nuclease targeting of the SH2 domain of SH2B3 was performed in the Dahl SS rat (SS/JrHsdMcwi) and resulted in an in-frame, 6 base pair deletion. Following salt stress, the SH2B3 mutants (SS-Sh2b3em1Mcwi) had significantly lower blood pressure (135 ± 1 mmHg vs 168 ± 8 mmHg, n=4-6/group) and attenuated kidney disease as indicated by albumin excretion rate (38 ± 7 mg/day vs 104 ± 9 mg/day) than the Dahl SS. Infiltration of leukocytes in the kidneys was significantly blunted in the SH2B3 mutant compared to the Dahl SS (5.4 ± 0.5 106/kidney vs 2.7 ± 0.3 106/kidney), and qPCR results show a significant reduction of IL-6 (2 fold) and MCP-1(1.8 fold) gene expression in the SH2B3 cortex. Vascular reactivity of mesenteric resistance arteries via wire myography in response serotonin or acetylcholine was not different between the SH2B3 mutant and Dahl SS. The mutation in SH2B3 appears to attenuate Dahl SS hypertension via inflammatory signaling and may reflect an underlying role for inflammation in human hypertension.
    No preview · Article · Apr 2014 · The FASEB Journal
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    ABSTRACT: Nuclear hormone receptors of the NR4A subgroup have been implicated in cancer, atherosclerosis, and metabolic disease. However, little is known about the role of these receptors in kidney health or disease. Nr4a1-deficient rats (Nr4a1(-/-)) developed on a genetic background susceptible to kidney injury (fawn-hooded hypertensive rat [FHH]) were evaluated for BP, proteinuria, renal function, and metabolic parameters from 4 to 24 weeks-of-age. By week 24, Nr4a1(-/-) rats exhibited significantly higher proteinuria (approximately 4-fold) and decreased GFR compared with FHH controls. The severity of tubular atrophy, tubular casts, and interstitial fibrosis increased significantly in Nr4a1(-/-) rats and was accompanied by a large increase in immune cell infiltration, predominantly macrophages and to a lesser extent T cells and B cells. Global transcriptome and network analyses at weeks 8, 16, and 24 identified several proinflammatory genes and pathways differentially regulated between strains. Bone marrow crosstransplantation studies demonstrated that kidney injury in Nr4a1(-/-) rats was almost completely rescued by bone marrow transplanted from FHH controls. In vitro, macrophages isolated from Nr4a1(-/-) rats demonstrated increased immune activation compared with FHH-derived macrophages. In summary, the loss of Nr4a1 in immune cells appears to cause the increased kidney injury and reduced renal function observed in the Nr4a1(-/-) model.
    No preview · Article · Apr 2014 · Journal of the American Society of Nephrology
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    ABSTRACT: The CD3 ζ chain (CD247), a gene involved in T-cell signaling, has been shown to associate with blood pressure in human genetic studies. To test the functional role of CD247 in hypertension and renal disease, zinc-finger nucleases targeting CD247 were injected into Dahl salt-sensitive (SS/JrHsdMcwi) embryos. The resulting 11-bp frameshift deletion in exon 1 of CD247 led to a predicted premature stop codon. Western blotting confirmed the absence of CD247 protein in the thymus, and flow cytometry (n=5-9 per group) demonstrated that the mutant rats (CD247(-/-)) have a >99% reduction in circulating CD3(+) T cells compared with littermate controls (CD247(+/+)). Studies were performed on age-matched, littermate male, CD247(+/+) and CD247(-/-) rats fed a 4.0% NaCl diet for 3 weeks. The infiltration of CD3(+) T cells into the kidney after high salt was significantly blunted in CD247(-/-) (1.4±0.4×10(5) cells per kidney) when compared with that in the CD247(+/+) (8.7±2.0×10(5) cells per kidney). Accompanying the reduced infiltration of T cells, mean arterial blood pressure was significantly lower in CD247(-/-) than in CD247(+/+) (134±1 versus 151±2 mm Hg). As an index of kidney disease, urinary albumin and protein excretion rates were significantly reduced in CD247(-/-) (17±1 and 62±2 mg/d, respectively) when compared with that in CD247(+/+) (49±3 and 121±5 mg/d, respectively). Glomerular and renal tubular damage were also attenuated in the CD247(-/-). These studies demonstrate that functional T cells are required for the full development of Dahl salt-sensitive hypertension and indicate that the association between CD247 and hypertension in humans may be related to altered immune cell function.
    No preview · Article · Mar 2014 · Hypertension
  • Satarupa Das · David L Mattson
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    ABSTRACT: Administration of exogenous L-Arginine (L-Arg) attenuates Angiotensin II (AngII)-mediated hypertension and kidney disease in rats. The present study assessed renal hemodynamics and pressure-diuresis-natriuresis in anesthetized rats infused with vehicle, AngII (20 ng/kg/min, iv) or AngII + L-Arg (300 μg/kg/min, iv). Increasing renal perfusion pressure (RPP) from approximately 100 to 140 mmHg resulted in a 9-10 fold increase in urine flow and sodium excretion rate in control animals. In comparison, AngII infusion significantly reduced renal blood flow (RBF) and glomerular filtration rate (GFR) by 40-42% and blunted the pressure-dependent increase in urine flow and sodium excretion rate by 54-58% at elevated RPP. Supplementation of L-Arg reversed the vasoconstrictor effects of AngII and restored pressure-dependent diuresis to levels not significantly different from control rats.Experiments in isolated aortic rings were performed to assess L-Arg effects on the vasculature. Dose-dependent contraction to AngII (10(-10) M to 10(-7) M) was observed with a maximal force equal to 27±3% of the response to 10(-5) M phenylephrine. Contraction to 10(-7) M AngII was blunted by 75±3% with 10(-4) M L-Arg. The influence of L-Arg to blunt AngII mediated contraction was eliminated by endothelial denudation or incubation with nitric oxide synthase inhibitors. Moreover, the addition of 10(-3) M cationic or neutral amino acids, which compete with L-Arg for cellular uptake, blocked the effect of L-Arg. Anionic amino acids did not influence the effects of L-Arg on AngII-mediated contraction. These studies indicate that L-Arg blunts AngII-mediated vascular contraction by an endothelial- and NOS-dependent mechanism involving cellular uptake of L-Arg. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2014 · Clinical and Experimental Pharmacology and Physiology
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    ABSTRACT: Transient receptor potential vanilloid type 4 (TRPV4) is an endothelial Ca(2+) entry channel contributing to endothelium-mediated dilation in conduit and resistance arteries. We investigated the role of TRPV4 in the regulation of blood pressure and endothelial function under hypertensive conditions. TRPV4-deficient (TRPV4(-/-)) and wild-type (WT) control mice were given l-NAME (0.5 g/L) in drinking water for 7 days or subcutaneously infused with angiotensin (Ang) II (600 ng/kg per minute) for 14 days, and blood pressure measured by radiotelemetry. TRPV4(-/-) mice had a lower baseline mean arterial pressure (MAP) (12-h daytime MAP, 94 ± 2 vs. 99 ± 2 mmHg in WT controls). l-NAME treatment induced a slightly greater increase in MAP in TRPV4(-/-) mice (day 7, 13 ± 4%) compared to WT controls (6 ± 2%), but Ang II-induced increases in MAP were similar in TRPV4(-/-) and WT mice (day 14, 53 ± 6% and 37 ± 11%, respectively, P < 0.05). Chronic infusion of WT mice with Ang II reduced both acetylcholine (ACh)-induced dilation (dilation to 10(-5) mol/L ACh, 71 ± 5% vs. 92 ± 2% of controls) and the TRPV4 agonist GSK1016790A-induced dilation of small mesenteric arteries (10(-8) mol/L GSK1016790A, 14 ± 5% vs. 77 ± 7% of controls). However, Ang II treatment did not affect ACh dilation in TRPV4(-/-) mice. Mechanistically, Ang II did not significantly alter either TRPV4 total protein expression in mesenteric arteries or TRPV4 agonist-induced Ca(2+) response in mesenteric endothelial cells in situ. These results suggest that TRPV4 channels play a minor role in blood pressure regulation in l-NAME- but not Ang II-induced hypertension, but may be importantly involved in Ang II-induced endothelial dysfunction.
    Full-text · Article · Jan 2014
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    ABSTRACT: Multiple genes and pathways are involved in the pathogenesis of hypertension. Epigenomic studies of hypertension are beginning to emerge and hold great promise of providing novel insights into the mechanisms underlying hypertension. Epigenetic marks or mediators including DNA methylation, histone modifications, and noncoding RNA can be studied at a genome or near-genome scale using epigenomic approaches. At the single gene level, several studies have identified changes in epigenetic modifications in genes expressed in the kidney that correlate with the development of hypertension. Systematic analysis and integration of epigenetic marks at the genome-wide scale, demonstration of cellular and physiological roles of specific epigenetic modifications, and investigation of inheritance are among the major challenges and opportunities for future epigenomic and epigenetic studies of hypertension.
    No preview · Article · Jul 2013 · Seminars in Nephrology
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    ABSTRACT: Historically, tools to assess renal function have been developed to investigate the physiology of the kidney in an experimental setting, and certain of these techniques have utility in evaluating renal function in the clinical setting. The following work will survey a spectrum of these tools, their applications and limitations in four general sections. The first is clearance, including evaluation of exogenous and endogenous markers for determining glomerular filtration rate, the adaptation of estimated glomerular filtration rate in the clinical arena, and additional clearance techniques to assess various other parameters of renal function. The second section deals with in vivo and in vitro approaches to the study of the renal microvasculature. This section surveys a number of experimental techniques including corticotomy, the hydronephrotic kidney, vascular casting, intravital charge coupled device videomicroscopy, multiphoton fluorescent microscopy, synchrotron-based angiography, laser speckle contrast imaging, isolated renal microvessels, and the perfused juxtamedullary nephron microvasculature. The third section addresses in vivo and in vitro approaches to the study of renal blood flow. These include ultrasonic flowmetry, laser-Doppler flowmetry, magnetic resonance imaging (MRI), phase contrast MRI, cine phase contrast MRI, dynamic contrast-enhanced MRI, blood oxygen level dependent MRI, arterial spin labeling MRI, x-ray computed tomography, and positron emission tomography. The final section addresses the methodologies of metabolic balance studies. These are described for humans, large experimental animals as well as for rodents. Overall, the various in vitro and in vivo topics and applications to evaluate renal function should provide a guide for the investigator or physician to understand and to implement the techniques in the laboratory or clinic setting. © 2013 American Physiological Society. Compr Physiol 3:165-200, 2013.
    No preview · Article · May 2013 · Comprehensive Physiology
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    ABSTRACT: Various stimuli, including hormones and growth factors, modulate epithelial sodium channels (ENaCs), which fine-tune Na(+) absorption in the kidney. Members of the EGF family are important for maintaining transepithelial Na(+) transport, but whether EGF influences ENaC, perhaps mediating salt-sensitive hypertension, is not well understood. Here, the ENaC inhibitor benzamil attenuated the development of hypertension in Dahl salt-sensitive rats. Feeding these salt-sensitive rats a high-salt diet led to lower levels of EGF in the kidney cortex and enhanced the expression and activity of ENaC compared with feeding a low-salt diet. To directly evaluate the role of EGF in the development of hypertension and its effect on ENaC activity, we infused EGF intravenously while continuously monitoring BP of the salt-sensitive rats. Infusion of EGF decreased ENaC activity, prevented the development of hypertension, and attenuated glomerular and renal tubular damage. Taken together, these findings indicate that cortical EGF levels decrease with a high-salt diet in salt-sensitive rats, promoting ENaC-mediated Na(+) reabsorption in the collecting duct and the development of hypertension.
    No preview · Article · Apr 2013 · Journal of the American Society of Nephrology
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    ABSTRACT: Hypertension and renal damage in Dahl SS rats are associated with increased infiltrating immune cells in the kidney. To examine the role of infiltrating immune cells in this disease process, a zinc finger nuclease targeting bases 672-706 of recombination activating gene 1 (Rag1) was injected into the pronucleus of Dahl SS (SS/JrHsdMcwi) strain embryos and implanted in pseudopregnant females. This strategy yielded a rat strain with a 13 base frame-shift mutation in the target region of Rag1 and a deletion of immunoreactive Rag1 protein in the thymus. Flow cytometry demonstrated that the Rag1 null mutant rats have a significant reduction in T- and B-lymphocytes in the circulation and spleen. Studies were performed on SS and Rag1 null rats fed a 4.0% NaCl diet for three weeks. The infiltration of T-cells into the kidney following high salt was significantly blunted in the Rag1 null rats (1.7±0.6 x 10(5) cells/kidney) compared to the Dahl SS (5.6±0.9 x 10(5) cells/kidney). Accompanying the reduction in infiltration of immune cells in the kidney, mean arterial blood pressure and urinary albumin excretion rat were significantly lower in Rag1 null mutants (158±3 mmHg and 60±16 mg/day, respectively) than in SS rats (180±11 mmHg and 251±37 mg/day). Finally, a histological analysis revealed that the glomerular and tubular damage in the kidneys of the SS rats fed high salt was also attenuated in the Rag1 mutants. These studies demonstrate the importance of renal infiltration of immune cells in the pathogenesis of hypertension and renal damage in Dahl SS rats.
    No preview · Article · Jan 2013 · AJP Regulatory Integrative and Comparative Physiology
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    Domagoj Mladinov · Yong Liu · David L Mattson · Mingyu Liang
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    ABSTRACT: MicroRNAs (miRNAs) play important roles in biological development and disease. Much less is known about their role in normal adult physiology. The proximal convoluted tubule (PCT) and the medullary thick ascending limb (mTAL) in the kidney consist of epithelial cells with different transport activities. We identified 55 possible miRNA-target pairs of which the miRNAs and their predicted target proteins, many of which are involved in epithelial transport, were inversely enriched in PCT and mTAL. Some miRNAs appeared to have synergistic effects on shared targets. miR-192 and its predicted target the β-1 subunit of Na+/K+-ATPase (Atp1b1), an enzyme providing the driving force for tubular transport, were inversely enriched in kidney regions. In mice, knockdown of miR-192 led to up-regulation of Atp1b1 protein. When mice were fed with a high-salt diet, knockdown of miR-192 blunted the adaptational increase of urine output. Interestingly, miR-192 appeared to target Atp1b1 through the 5′-, rather than 3′-untranslated region. The study suggests a novel physiological mechanism in which miR-192 suppresses Na+/K+-ATPase and contributes to renal handling of fluid balance. It supports an important role of miRNAs in determining cellular characteristics that may appear subtle yet are physiologically critical.
    Preview · Article · Dec 2012 · Nucleic Acids Research

Publication Stats

2k Citations
309.64 Total Impact Points


  • 1993-2015
    • Medical College of Wisconsin
      • Department of Physiology
      Milwaukee, Wisconsin, United States
  • 2014
    • University of Wisconsin - Milwaukee
      Milwaukee, Wisconsin, United States
  • 2008
    • University of California, Davis
      • Department of Pharmacology
      Davis, California, United States
  • 2004
    • University of North Carolina at Chapel Hill
      • Department of Pathology and Laboratory Medicine
      Chapel Hill, NC, United States
  • 2002
    • University of Maryland, Baltimore
      • Division of Nephrology
      Baltimore, MD, United States