V J Dzau

Duke University Medical Center, Durham, NC, United States

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Publications (470)3435.89 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Rationale: Cardiac progenitor cells (CPCs) are believed to differentiate into the major cell types of the heart; cardiomyocytes, smooth muscle cells, and endothelial cells. We have recently identified Abi3bp as a protein important for mesenchymal stem cell (MSC) biology. Since CPCs share several characteristics with MSCs we hypothesized that Abi3bp would similarly affect CPC differentiation and proliferation. Objective: To determine whether Abi3bp regulates CPC proliferation and differentiation. Methods and Results: In vivo, genetic ablation of the Abi3bp gene inhibited CPC differentiation whereas CPC number and proliferative capacity was increased. This correlated with adverse recovery following myocardial infarction. In vitro, CPCs, either isolated from Abi3bp knockout mice or expressing an Abi3bp shRNA construct, displayed a higher proliferative capacity and, under differentiating conditions, reduced expression of both early and late cardiomyocyte markers. Abi3bp controlled CPC differentiation via integrin-β1, PKCζ, and Akt. Conclusions: We have identified Abi3bp as a protein important for CPC differentiation and proliferation.
    Circulation Research 10/2014; · 11.86 Impact Factor
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    ABSTRACT: The therapeutic administration of microRNAs represents an innovative reprogramming strategy with which to advance cardiac regeneration and personalized medicine. Recently, a distinct set of microRNAs was found capable of converting murine fibroblasts to cardiomyocyte-like cells in vitro. Further treatment with JAK inhibitor I significantly enhanced the efficiency of the microRNA-mediated reprogramming (Jayawardena et al., Circ Res 110(11):1465-1473, 2012). This novel technique serves as an initial tool for switching the cell fate of cardiac fibroblasts toward the cardiomyocyte lineage using microRNAs. As the budding field of reprogramming biology develops, we hope that a thorough examination of the chemical, physical, and temporal parameters determining reprogramming efficiency and maturation will enable a better understanding of the mechanisms governing cardiac cell fate and provide new approaches for drug discovery and therapy for cardiovascular diseases.
    Methods in molecular biology (Clifton, N.J.) 01/2014; 1150:263-72. · 1.29 Impact Factor
  • New England Journal of Medicine 09/2013; 369(11):991-3. · 54.42 Impact Factor
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    ABSTRACT: There is a real need for innovation in health care delivery, as well as in medicine, to address related challenges of access, quality, and affordability through new and creative approaches. Health care environments must foster innovation, not just allowing it but actively encouraging it to happen anywhere and at every level in health care and medicine-from the laboratory, to the operating room, bedside, and clinics. This paper reviews the essential elements and environmental factors important for health-related innovation to flourish in academic health systems.The authors maintain that innovation must be actively cultivated by teaching it, creating "space" for and supporting it, and providing opportunities for its implementation. The authors seek to show the importance of these three fundamental principles and how they can be implemented, highlighting examples from across the country and their own institution.Health innovation cannot be relegated to a second-class status by the urgency of day-to-day operations, patient care, and the requirements of traditional research. Innovation needs to be elevated to a committed endeavor and become a part of an organization's culture, particularly in academic health centers.
    Academic medicine: journal of the Association of American Medical Colleges 08/2013; · 2.34 Impact Factor
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    ABSTRACT: Rationale: The regenerative capacity of the heart is markedly diminished shortly after birth coinciding with overall withdrawal of cardiomyocytes from cell cycle. Consequently, the adult mammalian heart has limited capacity to regenerate after injury. The discovery of factors that can induce cardiomyocyte proliferation is therefore of high interest and has been the focus of extensive investigation over the past years. Objective: We have recently identified C3orf58 as a novel Hypoxia and Akt induced Stem cell Factor (HASF) secreted from mesenchymal stem cells that can promote cardiac repair through cytoprotective mechanisms. Here, we tested the hypothesis that HASF can also contribute to cardiac regeneration by stimulating cardiomyocyte division and proliferation. Methods and Results: Neonatal ventricular cardiomyocytes were stimulated in culture for seven days with purified recombinant HASF protein. Compared to control untreated cells, HASF-treated neonatal cardiomyocytes exhibited 60% increase in DNA synthesis as measured by BrdU incorporation. These results were confirmed by immunofluorescence confocal microscopy showing a 50-100% increase in the number of cardiomyocytes in the mitotic and cytokinesis phases. Importantly, in vivo cardiac overexpression of HASF in a transgenic mouse model resulted in enhanced level of DNA synthesis and cytokinesis in neonatal and adult cardiomyocytes. These proliferative effects were modulated by a PI3K-AKT-CDK7 pathway as revealed by the use of PI3K pathway specific inhibitors and silencing of the Cdk7 gene. Conclusions: Our studies support the hypothesis that HASF induces cardiomyocyte proliferation via a PI3K-AKT-CDK7 pathway. The implications of this finding may be significant for cardiac regeneration biology and therapeutics.
    Circulation Research 06/2013; · 11.86 Impact Factor
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    ABSTRACT: The renin-angiotensin-aldosterone system (RAAS) regulates BP and salt-volume homeostasis. Juxtaglomerular (JG) cells synthesize and release renin, which is the first and rate-limiting step in the RAAS. Intense pathologic stresses cause a dramatic increase in the number of renin-producing cells in the kidney, termed JG cell recruitment, but how this occurs is not fully understood. Here, we isolated renal CD44(+) mesenchymal stem cell (MSC)-like cells and found that they differentiated into JG-like renin-expressing cells both in vitro and in vivo. Sodium depletion and captopril led to activation and differentiation of these cells into renin-expressing cells in the adult kidney. In summary, CD44(+) MSC-like cells exist in the adult kidney and can differentiate into JG-like renin-producing cells under conditions that promote JG cell recruitment.
    Journal of the American Society of Nephrology 06/2013; · 8.99 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSCs) transplanted into injured myocardium promote repair through paracrine mechanisms. We have previously shown that MSCs overexpressing AKT1 (Akt-MSCs) exhibit enhanced properties for cardiac repair. In this study, we investigated the relevance of Abi3bp towards MSC biology. Abi3bp formed extracellular deposits with expression controlled by Akt1 and ubiquitin-mediated degradation. Abi3bp knockdown/knockout stabilized focal adhesions and promoted stress-fiber formation. Furthermore, MSCs from Abi3bp knockout mice displayed severe deficiencies in osteogenic and adipogenic differentiation. Knockout or stable knockdown of Abi3bp increased MSC and Akt-MSC proliferation, promoting S-phase entry via cyclin-d1, ERK1/2 and Src. Upon Abi3bp binding to integrin-β1 Src associated with paxillin which inhibited proliferation. In vivo, Abi3bp knockout increased MSC number and proliferation in bone marrow, lung, and liver. In summary, we have identified a novel extracellular matrix protein necessary for the switch from proliferation to differentiation in MSCs.
    Stem Cells 05/2013; · 7.70 Impact Factor
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    ABSTRACT: Rationale: Regeneration of damaged cardiac tissue after injury presents a daunting challenge in cardiovascular medicine. Recent developments in reprogramming of somatic cells directly to cells of other lineages have raised the possibility of using this approach for cardiac regenerative therapy. Our group recently demonstrated successful miRNA mediated cardiac reprogramming in vitro and in vivo using a combination of miRNAs 1, 133, 206 and 499. Although, the molecular mechanisms underlying miRNA mediated fibroblast reprogramming to cardiomyocytes are yet unknown, accumulating evidence suggest that reprogramming acts through distinct phases and that histone modifications play an important role in these processes. Objective: Identify key genes involved in initiating miRNA mediated reprogramming via histone modifications. Methods and Results: For this, we analyzed the expression levels of 81 different genes involved in chromatin modification 4 days after miRNA transfection using PCR arrays. This analysis revealed that 6 of the 81 tested genes showed differential gene expression (-1.5-fold and p <0.02). JAK inhibitor-1 treatment, known for increasing reprogramming efficiency, further enhanced gene expression changes in 5 of these 6 genes. Setdb2, an H3K9 methyltransferase, was one of the most down-regulated targets 4 days after miRNA transfection (-1.4 fold, p<0.001). This effect was enhanced further when miRNAs were combined with the JAK inhibitor-1 (-2.6 fold, p<0.001). Silencing of Setdb2 using siRNAs further accentuated miRNA cardiac reprogramming as measured by cardiac transcription factor expression at 3 days and 6 days post treatment. Similar trends were observed by FACS analysis detecting increased percentage of αMHC-positive cells in siRNA treated fibroblasts compared to control treated only with the miRNA combination. Interestingly, our data showed that Setdb2 silencing alone was sufficient to initiate cardiac reprogramming, suggesting that Setdb2 might play a crucial role in defining cardiac cell fate. Conclusion: In conclusion our results indicate that Setdb2 down-regulation plays an important role in the direct reprogramming of fibroblasts to cardiomyocyte-like cells.
    BCVS 2013, Las Vegas, NV; 05/2013
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    ABSTRACT: Despite advances in the treatment of acute tissue ischemia significant challenges remain in effective cytoprotection from ischemic cell death. It has been documented that injected stem cells, such as mesenchymal stem cells (MSCs), can confer protection to ischemic tissue through the release of paracrine factors. The study of these factors is essential for understanding tissue repair and the development of new therapeutic approaches for regenerative medicine. We have recently shown that a novel factor secreted by MSCs, which we called HASF (Hypoxia and Akt induced Stem cell Factor), promotes cardiomyocyte proliferation. In this study we show that HASF has a cytoprotective effect on ischemia induced cardiomyocyte death. We assessed whether HASF could potentially be used as a therapeutic agent to prevent the damage associated with myocardial infarction. In vitro treatment of cardiomyocytes with HASF protein resulted in decreased apoptosis; TUNEL positive nuclei were fewer in number, and caspase activation and mitochondrial pore opening were inhibited. Purified HASF protein was injected into the heart immediately following myocardial infarction. Heart function was found to be comparable to sham operated animals one month following injury and fibrosis was significantly reduced. In vivo and in vitro HASF activated protein kinase C ε (PKCε). Inhibition of PKCε blocked the HASF effect on apoptosis. Furthermore, the beneficial effects of HASF were lost in mice lacking PKCε. Collectively these results identify HASF as a protein of significant therapeutic potential, acting in part through PKCε.
    Journal of Molecular and Cellular Cardiology 01/2013; · 5.15 Impact Factor
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    ABSTRACT: The Duke Medicine Graduate Medical Education Quasi-Endowment, established in 2006, provides infrastructure support and encourages educational innovation. The authors describe Duke's experience with the "grassroots innovation" part of the fund, the Duke Innovation Fund, and discuss the Innovation Fund's processes for application, review, and implementation, and also outcomes, impact, and intended and unintended consequences.In the five years of the Innovation Fund described (2007-2011), 105 projects have been submitted, and 78 have been funded. Thirty-seven projects have been completed. Approved funding ranged from $2,363 to $348,750, with an average award of $66,391. This represents 42% of funding originally requested. Funding could be requested for a period of 6 months to 3 years. The average duration of projects was 27 months, with a range from 6 months to 36 months. Eighty percent of projects were completed on time. Two projects were closed because of lack of progress and failure to adhere to reporting requirements. Thirty-nine are ongoing.Program directors report great success in meeting project outcomes and concrete impacts on resident and faculty attitudes and performance. Ninety-two percent report that their projects would have never been accomplished without this funding. Projects have resulted in at least 68 posters, abstracts, and peer-reviewed presentations. At least 12 peer-reviewed manuscripts were published.There has been tremendous diversity of projects; all 13 clinical departments have been represented. Interdepartmental and intradepartmental program cooperation has increased. This modest seed money has resulted in demonstrable sustainable impacts on teaching and learning, and increased morale and scholarly recognition.
    Academic medicine: journal of the Association of American Medical Colleges 12/2012; · 2.34 Impact Factor
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    ABSTRACT: Introduction: Direct conversion of injured heart tissue to functional cardiomyocyte in situ represents an exciting approach for cardiac regeneration. We have recently shown that the combination of miRNAs 1, 133, 208 and 499 were able to reprogram mouse cardiac fibroblasts in vitro and in vivo to cardiomyocyte like cells. Here, we investigate the mechanisms involved in these processes as well as explore the feasibility of this approach in reprogramming human fibroblasts towards the cardiomyocyte fate. Methods and Results: Expression analysis miRNA transfected fibroblast demonstrated rapid induction (1-2 days) of primitive cardiac mesodermal marker Mesp2 but no change in the pluripotency markers Oct4 and Nanog suggesting that reprogramming results from a direct switch to cardiomyocyte progenitor state. Further microarray analysis using the Affymetrix GeneChip Mouse Genome 430 2.0 Array revealed that 1200 genes were differentially regulated between miRNA treated and control cardiac fibroblasts (P<0.01). This list was highly enriched for transcription factors and chromatin remodeling modulators (125 genes). HDAC2, a histone deacetylase that was recently associated with reprogramming of fibroblasts to iPS cells, was the only histone deacetylase that showed significant change upon treatment with the miRNA combination (decreased nearly 95%). These results were corroborated by qRT-PCR. Clustering analysis consistently altered expression of a sub-cluster of 5 genes (with functional relevance to HDAC2, further highlighting the potential importance of HDAC in modulating the miRNA effects directly and/or indirectly. Finally, to explore the feasibility of the miRNA approach to reprogram human fibroblasts, we transiently transfected BJ cells with the microRNA combination. Our preliminary results indicate that combination microRNA treatment of human fibroblasts results in the upregulation of early cardiomyocyte markers such as Mef2. Conclusion: Our data provide insights into the mechanisms of microRNA mediated cardiac reprogramming, indicating direct conversion and the potential role of epigenetic modulation.
    American Heart Association (AHA) Scientific Sessions, Los Angeles; 11/2012
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    ABSTRACT: Repopulation of the injured heart with new, functional cardiomyocytes remains a daunting challenge for cardiac regenerative medicine. An ideal therapeutic approach would involve an effective method at achieving direct conversion of injured areas to functional tissue in situ. The aim of this study was to develop a strategy that identified and evaluated the potential of specific micro (mi)RNAs capable of inducing reprogramming of cardiac fibroblasts directly to cardiomyocytes in vitro and in vivo. Using a combinatorial strategy, we identified a combination of miRNAs 1, 133, 208, and 499 capable of inducing direct cellular reprogramming of fibroblasts to cardiomyocyte-like cells in vitro. Detailed studies of the reprogrammed cells demonstrated that a single transient transfection of the miRNAs can direct a switch in cell fate as documented by expression of mature cardiomyocyte markers, sarcomeric organization, and exhibition of spontaneous calcium flux characteristic of a cardiomyocyte-like phenotype. Interestingly, we also found that miRNA-mediated reprogramming was enhanced 10-fold on JAK inhibitor I treatment. Importantly, administration of miRNAs into ischemic mouse myocardium resulted in evidence of direct conversion of cardiac fibroblasts to cardiomyocytes in situ. Genetic tracing analysis using Fsp1Cre-traced fibroblasts from both cardiac and noncardiac cell sources strongly suggests that induced cells are most likely of fibroblastic origin. The findings from this study provide proof-of-concept that miRNAs have the capability of directly converting fibroblasts to a cardiomyocyte-like phenotype in vitro. Also of significance is that this is the first report of direct cardiac reprogramming in vivo. Our approach may have broad and important implications for therapeutic tissue regeneration in general.
    Circulation Research 04/2012; 110(11):1465-73. · 11.86 Impact Factor
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    ABSTRACT: Globalization is having a growing impact on health and health care, presenting challenges as well as opportunities for the U.S. health care industry in general and for academic health science systems (AHSSs) in particular. The authors believe that AHSSs must develop long-term strategies that address their future role in global medicine. AHSSs should meet global challenges through planning, engagement, and innovation that combine traditional academic activities with entrepreneurial approaches to health care delivery, research, and education, including international public-private partnerships. The opportunities for U.S.-based AHSSs to be global health care leaders and establish partnerships that improve health locally and globally more than offset the potential financial, organizational, politico-legal, and reputational risks that exist in the global health care arena. By examining recent international activities of leading AHSSs, the authors review the risks and the critical factors for success and discuss external policy shifts in workforce development and accreditation that would further support the growth of global medicine.
    Academic medicine: journal of the Association of American Medical Colleges 09/2011; 86(9):1093-9. · 2.34 Impact Factor
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    ABSTRACT: The rapidly changing field of medicine demands that future physician-leaders excel not only in clinical medicine but also in the management of complex health care enterprises. However, many physicians have become leaders "by accident," and the active cultivation of future leaders is required. Addressing this need will require multiple approaches, targeting trainees at various stages of their careers, such as degree-granting programs, residency and fellowship training, and career and leadership development programs. Here, the authors describe a first-of-its-kind graduate medical education pathway at Duke Medicine, the Management and Leadership Pathway for Residents (MLPR). This program was developed for residents with both a medical degree and management training. Created in 2009, with its first cohort enrolled in the summer of 2010, the MLPR is intended to help catalyze the emergence of a new generation of physician-leaders. The program will provide physicians-in-training with rigorous clinical exposure along with mentorship and rotational opportunities in management to accelerate the development of critical leadership and management skills in all facets of medicine, including care delivery, research, and education. To achieve this, the MLPR includes 15 to 18 months of project-based rotations under the guidance of senior leaders in many disciplines including finance, patient safety, health system operations, strategy, and others. Developing both clinical and management skill sets during graduate medical education holds the promise of engaging future leaders of health care at an early career stage, keeping more MD-MBA graduates within health care, and creating a bench of talented future physician-executives.
    Academic medicine: journal of the Association of American Medical Colleges 03/2011; 86(5):575-9. · 2.34 Impact Factor
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    ABSTRACT: Stem cells play an important role in restoring cardiac function in the damaged heart. In order to mediate repair, stem cells need to replace injured tissue by differentiating into specialized cardiac cell lineages and/or manipulating the cell and molecular mechanisms governing repair. Despite early reports describing engraftment and successful regeneration of cardiac tissue in animal models of heart failure, these events appear to be infrequent and yield too few new cardiomyocytes to account for the degree of improved cardiac function observed. Instead, mounting evidence suggests that stem cell mediated repair takes place via the release of paracrine factors into the surrounding tissue that subsequently direct a number of restorative processes including myocardial protection, neovascularization, cardiac remodeling, and differentiation. The potential for diverse stem cell populations to moderate many of the same processes as well as key paracrine factors and molecular pathways involved in stem cell-mediated cardiac repair will be discussed in this review. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".
    Journal of Molecular and Cellular Cardiology 02/2011; 50(2):280-9. · 5.15 Impact Factor
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    ABSTRACT: The use of stem cells for tissue regeneration and repair is advancing both at the bench and bedside. Stem cells isolated from bone marrow are currently being tested for their therapeutic potential in a variety of clinical conditions including cardiovascular injury, kidney failure, cancer, and neurological and bone disorders. Despite the advantages, stem cell therapy is still limited by low survival, engraftment, and homing to damage area as well as inefficiencies in differentiating into fully functional tissues. Genetic engineering of mesenchymal stem cells is being explored as a means to circumvent some of these problems. This review presents the current understanding of the use of genetically engineered mesenchymal stem cells in human disease therapy with emphasis on genetic modifications aimed to improve survival, homing, angiogenesis, and heart function after myocardial infarction. Advancements in other disease areas are also discussed.
    Human gene therapy 11/2010; 21(11):1513-26. · 4.20 Impact Factor
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    ABSTRACT: Secreted frizzled related protein 2 (Sfrp2) is known as an inhibitor for the Wnt signaling. In recent studies, Sfrp2 has been reported to inhibit the activity of Xenopus homolog of mammalian Tolloid-like 1 metalloproteinase. Bone morphogenic protein 1 (Bmp1)/Tolloid-like metalloproteinase plays a key role in the regulation of collagen biosynthesis and maturation after tissue injury. Here, we showed both endogenous Sfrp2 and Bmp1 protein expressions were up-regulated in rat heart after myocardial infarction (MI). We hypothesize that Sfrp2 could inhibit mammalian Bmp1 activity and, hence, the exogenous administration of Sfrp2 after MI would inhibit the deposition of mature collagen and improve heart function. Using recombinant proteins, we demonstrated that Sfrp2, but not Sfrp1 or Sfrp3, inhibited Bmp1 activity in vitro as measured by a fluorogenic peptide based procollagen C-proteinase activity assay. We also demonstrated that Sfrp2 at high concentration inhibited human and rat type I procollagen processing by Bmp1 in vitro. We further showed that exogenously added Sfrp2 inhibited type I procollagen maturation in primary cardiac fibroblasts. Two days after direct injection into the rat infarcted myocardium, Sfrp2 inhibited MI-induced type I collagen deposition. As early as 2 wk after injection, Sfrp2 significantly reduced left ventricular (LV) fibrosis as shown by trichrome staining. Four weeks after injection, Sfrp2 prevented the anterior wall thinning and significantly improved cardiac function as revealed by histological analysis and echocardiographic measurement. Our study demonstrates Sfrp2 at therapeutic doses can inhibit fibrosis and improve LV function at a later stage after MI.
    Proceedings of the National Academy of Sciences 11/2010; 107(49):21110-5. · 9.81 Impact Factor
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    ABSTRACT: Although mesenchymal stem cell (MSC) transplantation has been shown to promote cardiac repair in acute myocardial injury in vivo, its overall restorative capacity appears to be restricted mainly because of poor cell viability and low engraftment in the ischemic myocardium. Specific chemokines are upregulated in the infarcted myocardium. However the expression levels of the corresponding chemokine receptors (eg, CCR1, CXCR2) in MSCs are very low. We hypothesized that this discordance may account for the poor MSC engraftment and survival. To determine whether overexpression of CCR1 or CXCR2 chemokine receptors in MSCs augments their cell survival, migration and engraftment after injection in the infarcted myocardium. Overexpression of CCR1, but not CXCR2, dramatically increased chemokine-induced murine MSC migration and protected MSC from apoptosis in vitro. Moreover, when MSCs were injected intramyocardially one hour after coronary artery ligation, CCR1-MSCs accumulated in the infarcted myocardium at significantly higher levels than control-MSCs or CXCR2-MSCs 3 days postmyocardial infarction (MI). CCR1-MSC-injected hearts exhibited a significant reduction in infarct size, reduced cardiomyocytes apoptosis and increased capillary density in injured myocardium 3 days after MI. Furthermore, intramyocardial injection of CCR1-MSCs prevented cardiac remodeling and restored cardiac function 4 weeks after MI. Our results demonstrate the in vitro and in vivo salutary effects of genetic modification of stem cells. Specifically, overexpression of chemokine receptor enhances the migration, survival and engraftment of MSCs, and may provide a new therapeutic strategy for the injured myocardium.
    Circulation Research 04/2010; 106(11):1753-62. · 11.86 Impact Factor
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    Zhiping Zhang, Victor J Dzau
    Hypertension 03/2010; 55(5):1086-7. · 6.87 Impact Factor
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    ABSTRACT: Renin is a key enzyme for cardiovascular and renal homeostasis and is produced by highly specialized endocrine cells in the kidney, known as juxtaglomerular (JG) cells. The nature and origin of these cells remain as mysteries. Previously, we have shown that the nuclear hormone receptor liver X receptor-alpha (LXRalpha) is a major transcriptional regulator of the expression of renin, c-myc, and other genes involved with growth/differentiation. In this study we test the hypothesis that LXRalpha plays an important role not only in renin expression but also in renin-containing cell differentiation, specifically from the mesenchymal stem cell (MSC), which may be the origin of the JG cell. Indeed, our data demonstrated that LXRalpha activation by its ligands or cAMP stimulated renin gene expression in both murine and human MSCs. Furthermore, sustained cAMP stimulation of murine MSCs overexpressing LXRalpha led to their differentiation into JG-like cells expressing renin and alpha-smooth muscle actin. These MSC-derived JG-like cells contained renin in secretory granules and released active renin in response to cAMP. In conclusion, the activation of LXRalpha stimulates renin expression and induces MSCs differentiation into renin-secreting, JG-like cells. Our results suggest that the MSC may be the origin of the juxtaglomerular cell and provide insight into novel understanding of pathophysiology of the renin-angiotensin system.
    Journal of Biological Chemistry 01/2010; 285(16):11974-11982. · 4.65 Impact Factor

Publication Stats

26k Citations
3,435.89 Total Impact Points

Institutions

  • 2005–2013
    • Duke University Medical Center
      • • Department of Medicine
      • • Department of Community and Family Medicine
      • • Division of Cardiology
      Durham, NC, United States
    • University of São Paulo
      San Paulo, São Paulo, Brazil
  • 2011
    • University of Pavia
      Ticinum, Lombardy, Italy
    • North Carolina Clinical Research
      Raleigh, North Carolina, United States
  • 2007–2009
    • Duke University
      Durham, North Carolina, United States
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2004–2007
    • Queen's University
      • Department of Physiology
      Kingston, Ontario, Canada
    • University of Glasgow
      • Institute of Cardiovascular and Medical Sciences
      Glasgow, Scotland, United Kingdom
    • Yokohama City University
      • Department of Medicine
      Yokohama, Kanagawa, Japan
    • Morehouse School of Medicine
      Atlanta, Georgia, United States
  • 1982–2007
    • Brigham and Women's Hospital
      • • Department of Medicine
      • • Center for Brain Mind Medicine
      • • Division of Cardiovascular Medicine
      Cambridge, MA, United States
    • Harvard Medical School
      • Department of Medicine
      Boston, MA, United States
    • Ochsner
      New Orleans, Louisiana, United States
  • 2002–2004
    • University of California, San Francisco
      • Division of Adult Cardiothoracic Surgery
      San Francisco, CA, United States
  • 2003
    • Houston Methodist Hospital
      Houston, Texas, United States
  • 2001–2002
    • University of Toronto
      • Department of Laboratory Medicine and Pathobiology
      Toronto, Ontario, Canada
  • 1996–2002
    • Osaka University
      • • Division of Gene Therapy Science
      • • Division of Cellular and Molecular Biology
      Ōsaka-shi, Osaka-fu, Japan
  • 1999–2001
    • Justus-Liebig-Universität Gießen
      Gieben, Hesse, Germany
  • 2000
    • University of Maryland, Baltimore
      • Department of Medicine
      Baltimore, MD, United States
  • 1992–1997
    • Stanford Medicine
      • • Falk Cardiovascular Research Center
      • • Department of Medicine
      • • Division of Cardiovascular Medicine
      Stanford, California, United States
    • University of Florida
      Gainesville, Florida, United States
  • 1990–1996
    • Stanford University
      • • Falk Cardiovascular Research Center
      • • Division of Cardiovascular Medicine
      Stanford, CA, United States
    • University of Minnesota Medical Center, Fairview
      Minneapolis, Minnesota, United States
  • 1993
    • Center of Kidney and High Blood Pressure Diseases
      Igersheim, Baden-Württemberg, Germany
    • Universität Regensburg
      • Lehrstuhl für Innere Medizin II
      Regensburg, Bavaria, Germany
  • 1991
    • Massachusetts General Hospital
      • Division of Pediatric Urology
      Boston, MA, United States