Cyclic AMP stimulates renin gene transcription in juxtaglomerular cells

Klar, Jürgen; Sandner, Peter; Müller, Markus; Kurtz, Armin

doi:10.1007/s00424-002-0818-9

Cited by 60 publications

(77 citation statements)

References 39 publications

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“…10 The primers for renin and ␤-actin were used as described. 11 The sequences of the primers used for the amplification of dynamin1, dynamin2, MINT, and nucleolin are available on request.…”

Section: Reverse Transcriptase Reaction and Quantitative Pcr Analysismentioning

confidence: 99%

“…11 The 3 TGACϪ sites from Ϫ2698 to Ϫ2695 bp, from Ϫ2674 to Ϫ2671 bp, and from Ϫ2657 to Ϫ2654 bp in the 2.8-kb fragment were deleted with the QuikChange site-directed mutagenesis kit (Stratagene).…”

Section: Plasmid Constructsmentioning

confidence: 99%

“…11 The gel shift reaction (10 L) was run as described. 11 After electrophoresis at room temperature, the gels were dried for autoradiography.…”

Section: Electrophoretic Mobility-shift Assaymentioning

confidence: 99%

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Calcium Inhibits Renin Gene Expression by Transcriptional and Posttranscriptional Mechanisms

et al. 2005

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Abstract-The aim of this study was to investigate the role of cytosolic calcium for renin gene expression in juxtaglomerular cells. For this purpose, we used the immortalized juxtaglomerular mouse cell line As4.1. To increase cytosolic calcium concentration, we treated the cells with thapsigargin and cyclopiazonic acid, inhibitors of the endoplasmatic reticulum CaϪ ATPase. Thapsigargin and cyclopiazonic acid inhibited renin gene expression in a characteristic time and concentration-dependent manner. This effect was concentration-dependently blocked by BAPTA-AM, an intracellular Ca 2ϩ chelator. Pharmacological blocking of protein kinase C activity by calphostin, Gö6976, and Gö6983 did not change the effect of thapsigargin on renin gene expression. Experiments with renin1 C -promoter-reporter constructs revealed that thapsigargin inhibited renin gene transcription. Analysis of deletion constructs of the renin1 C promoter indicated that regulatory elements involved in the calcium-mediated inhibition of renin gene transcription are located in the enhancer region of the renin gene and that Ն3 transcription factor-binding sites are involved in this process. In addition, thapsigargin reduced the renin mRNA half-life from 10 hours (control conditions) to 4 hours. Knockdown studies with small interfering RNA directed to dynamin-1 mRNA revealed that dynamin-1 is likely to be involved in the calcium-mediated destabilization of renin mRNA. These data suggest that calcium inhibits renin gene expression in juxtaglomerular cells via a concerted action of inhibition of renin gene transcription and destabilization of renin mRNA. Key Words: calcium Ⅲ renin-angiotensin-aldosterone system Ⅲ thapsigargin Ⅲ mRNA stability T he renin-angiotensin-aldosterone system is a major regulatory system controlling extracellular fluid volume and blood pressure. The activity of the renin-angiotensin-aldosterone system is rate limited by the activity of the protease renin. 1 Renin itself is also regulated by a variety of factors. In the past few years, our knowledge has increased substantially about the regulation of renin gene expression at the cellular level. [2][3][4] For the transcription of the mouse renin gene, 2 critical regions, a proximal promoter region at Ϫ197 to Ϫ50 bp and an enhancer element at Ϫ2866 to Ϫ2625 bp, have been identified. 4 Also, the regulation of the renin mRNA stability is influenced by various factors, among these, interacting partner proteins like MINT, dynamin, or nucleolin have been found to be involved in the stabilization process of the renin mRNA. 5 The focus of our study was to investigate the role of calcium in the regulation of renin gene expression. This is of particular interest, because vasoactive peptides like angiotensin II or endothelin-1, which are known to be direct regulators of renin gene expression, activate the phospholipase C via a G protein-coupled receptor and, in turn, increase inositol triphosphate and diacylglycerol (DAG). 3 Whereas DAG is known to activate protein kinase C, inositol triphosp...

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Section: Reverse Transcriptase Reaction and Quantitative Pcr Analysismentioning

confidence: 99%

Section: Plasmid Constructsmentioning

confidence: 99%

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Calcium Inhibits Renin Gene Expression by Transcriptional and Posttranscriptional Mechanisms

et al. 2005

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“…In the Ren-1c promoter, a CRE at Ϫ2688 is bound by CREB/CREM and is essential for the high level of basal renin expression in As4.1 cells (13). cAMP has been reported to stimulate renin gene transcription in As4.1 cells (23).…”

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1,25-Dihydroxyvitamin D3 Suppresses Renin Gene Transcription by Blocking the Activity of the Cyclic AMP Response Element in the Renin Gene Promoter

Yuan

Wei

Kong

et al. 2007

Journal of Biological Chemistry

435

348

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“…RT-PCR was used to determine the expression of receptors corresponding to several adhesion molecules/ECM proteins, and chemokines/ cytokines identified through profiling. RNA samples from murine peripheral blood mononuclear cells (PBMCs), juxtaglomerular cells (JGCs, from JG cell line As4.1; American Type Culture Collection, Manassas, VA) (Klar et al, 2002), vascular smooth muscle cells (VSMCs, isolated from murine thoracic aortae), and skin keratinocytes were used for comparison. …”

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Mesenchymal Stem Cells Use Integrin β1 Not CXC Chemokine Receptor 4 for Myocardial Migration and Engraftment

Huang

et al. 2007

MBoC

217

145

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Recent evidence has demonstrated the importance of bone marrow-derived mesenchymal stem cells (BM-MSCs) in the repair of damaged myocardium. The molecular mechanisms of engraftment and migration of BM-MSCs in the ischemic myocardium are unknown. In this study, we developed a functional genomics approach toward the identification of mediators of engraftment and migration of BM-MSCs within the ischemic myocardium. Our strategy involves microarray profiling (>22,000 probes) of ischemic hearts, complemented by reverse transcription-polymerase chain reaction and fluorescence-activated cell sorting of corresponding adhesion molecule and cytokine receptors in BM-MSCs to focus on the coexpressed pairs only. Our data revealed nine complementary adhesion molecules and cytokine receptors, including integrin ␤1, integrin ␣4, and CXC chemokine receptor 4 (CXCR4). To examine their functional contributions, we first blocked selectively these receptors by preincubation of BM-MSCs with specific neutralizing antibodies, and then we administered these cells intramyocardially. A significant reduction in the total number of BM-MSC in the infarcted myocardium was observed after integrin ␤1 blockade but not integrin ␣4 or CXCR4 blockade. The latter observation is distinctively different from that reported for hematopoietic stem cells (HSCs). Thus, our data show that BM-MSCs use a different pathway from HSCs for intramyocardial trafficking and engraftment. INTRODUCTIONCardiac repair and remodeling after ischemic injury involves myocyte hypertrophy, collagen deposition, and possibly ventricular dilatation (Sutton and Sharpe, 2000). Recent provocative data suggest that stem cells, either resident in the heart or originating from the bone marrow, may play an important role in the repair and regeneration of the injured myocardium (Anversa and Nadal-Ginard, 2002). We and others have shown that intramyocardial transplantation of bone marrow-derived stem cells (BMSCs) can promote cardiac repair with resulting functional improvement and reduced infarct size (Kocher et al., 2001;Mangi et al., 2003;Amado et al., 2005). In addition to direct transplantation, mobilization of BMSCs with cytokines such as granulocytecolony stimulating factor (G-CSF) and stem cell factor has been reported to enhance myocardial repair and improve cardiac function (Anversa and Nadal-Ginard, 2002;Askari et al., 2003). However, in a recent trial, the subcutaneous administration of G-CSF after acute myocardial infarction (MI) did not lead to further improvement in ventricular function compared with conventional treatment (Ripa et al., 2006). These controversial findings suggest the need to understand the molecular mechanisms involved with stem cell migration and engraftment into the infarcted myocardium.It has been reported that hematopoietic stem cells (HSCs) migrate in response to stromal-derived factor (SDF)-1␣, the ligand for the CXC chemokine receptor 4 (CXCR4) (Wright et al., 2002), and the up-regulation of SDF-1 in the ischemic myocardium mediates homing of HSCs vi...

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Cyclic AMP stimulates renin gene transcription in juxtaglomerular cells

Cited by 60 publications

References 39 publications

Calcium Inhibits Renin Gene Expression by Transcriptional and Posttranscriptional Mechanisms

Calcium Inhibits Renin Gene Expression by Transcriptional and Posttranscriptional Mechanisms

1,25-Dihydroxyvitamin D3 Suppresses Renin Gene Transcription by Blocking the Activity of the Cyclic AMP Response Element in the Renin Gene Promoter

Mesenchymal Stem Cells Use Integrin β1 Not CXC Chemokine Receptor 4 for Myocardial Migration and Engraftment

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