The Bradykinin B2 Receptor Gene Is a Target of Angiotensin II Type 1 Receptor Signaling

Shen, Bing; Harrison‐Bernard, Lisa M.; Fuller, Andrew; Vanderpool, Vanessa; Saifudeen, Zubaida; El‐Dahr, Samir S.

doi:10.1681/asn.2006101127

Cited by 38 publications

(39 citation statements)

References 40 publications

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“…Immunofluorescence Staining of mK4 cells-Immunofluorescence staining of mK4 cells was performed as described previously (51). The primary antibodies used include an anti-HDAC1 antibody (rabbit polyclonal, 1:100, BioVision) and an anti-HDAC2 antibody (rabbit polyclonal, 1:100, BioVision).…”

Section: Rt-pcr and Real Time Rt-pcr-totalmentioning

confidence: 99%

Histone Deacetylase (HDAC) Activity Is Critical for Embryonic Kidney Gene Expression, Growth, and Differentiation

Chen

Bellew

Xiao

et al. 2011

Journal of Biological Chemistry

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Histone deacetylases (HDACs) regulate fundamental biological processes such as cellular proliferation, differentiation, and survival via genomic and nongenomic effects. This study examined the importance of HDAC activity in the regulation of gene expression and differentiation of the developing mouse kidney. Class I HDAC1-3 and class II HDAC4, -7, and -9 genes are developmentally regulated. Moreover, HDAC1-3 are highly expressed in nephron precursors. Short term treatment of cultured mouse embryonic kidneys with HDAC inhibitors (HDACi) induced global histone H3 and H4 hyperacetylation and H3K4 hypermethylation. However, genome-wide profiling revealed that the HDAC-regulated transcriptome is restricted and encompasses regulators of the cell cycle, Wnt/␤-catenin, TGF-␤/Smad, and PI3K-AKT pathways. Further analysis demonstrated that base-line expression of key developmental renal regulators, including Osr1, Eya1, Pax2/8, WT1, Gdnf, Wnt9b, Sfrp1/2, and Emx2, is dependent on intact HDAC activity. Treatment of cultured embryonic kidney cells with HDACi recapitulated these gene expression changes, and chromatin immunoprecipitation assays revealed that HDACi is associated with histone hyperacetylation of Pax2/Pax8, Gdnf, Sfrp1, and p21. Gene knockdown studies demonstrated that HDAC1 and HDAC2 play a redundant role in regulation of Pax2/8 and Sfrp1 but not Gdnf. Long term treatment of embryonic kidneys with HDACi impairs the ureteric bud branching morphogenesis program and provokes growth arrest and apoptosis. We conclude that HDAC activity is critical for normal embryonic kidney homeostasis, and we implicate class I HDACs in the regulation of early nephron gene expression, differentiation, and survival.Kidney development depends on reciprocal inductive interactions between the metanephric mesenchyme (MM), 4 a specified region in the caudal intermediate mesoderm, and the ureteric bud (UB), an epithelial outgrowth from the Wolffian (nephric) duct (1-3). Recent years have witnessed significant progress in our understanding of the gene regulatory networks of early kidney development (3-6). For example, the Osr1/ Eya1/Pax2/Six/Sall/WT1/Hoxd11 gene regulatory network specifies the MM and is absolutely required for expression of glia-derived neurotrophic factor (Gdnf) (7,8). Gdnf, in turn, is essential for UB outgrowth and subsequent branching (9 -11).Gdnf acts via activation of a c-Ret/PI3K/ERK-dependent gene network (Wnt11, Spry1, Etv4, Etv5, Cxcr4, Myb, Met, and Mmp14) in UB tip cells to control the branching morphogenesis program (12-14). Various growth factor/receptor signaling pathways, including FGFs, bone morphogenic proteins, VEGF, semaphorins, hepatocyte growth factor, EGF, among others, share signaling components with the c-Ret pathway and are required for optimal metanephric growth and patterning (15)(16)(17)(18)(19)(20)(21)(22). Following induction of the MM, activation of the Wnt/␤-catenin signaling pathway plays a key role in nephrogenesis. Release of Wnt9b from the UB branches triggers a ␤-catenindependent mo...

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Section: Rt-pcr and Real Time Rt-pcr-totalmentioning

confidence: 99%

Histone Deacetylase (HDAC) Activity Is Critical for Embryonic Kidney Gene Expression, Growth, and Differentiation

Chen

Bellew

Xiao

et al. 2011

Journal of Biological Chemistry

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“…AT1R-and B2R signalling fuctionally interact on many levels in vitro and in vivo and they have important biological effects that are opposing each other (30,31). In a series of reports Abdalla,…”

Section: At1/b2 Receptor Heterodimerizationmentioning

confidence: 99%

“…The biological significance of heterodimerization could also be profound, since it will add an additional layer of complexity to the understanding of how 7TM receptors are activated, and it provides yet another link for cross-talk between different receptor systems (30,31). Even though much data present today suggests that 7TM receptor dimerization do occur and may have a functional purpose, the exact role of dimerization has not yet been defined.…”

Section: Introductionmentioning

confidence: 99%

Functional interactions between 7TM receptors in the Renin-Angiotensin System—Dimerization or crosstalk?

Lyngsø

Erikstrup

Hansen

2009

Molecular and Cellular Endocrinology

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Abstract:The Renin-Angiotensin System (RAS) is important for the regulation of cardiovascular physiology, where it controls blood pressure, and salt-and water homeostasis. Dysregulation of RAS can lead to severe diseases including hypertension, diabetic nephropathy, and cardiac arrhythmia, and -failure.The importance of the RAS is clearly emphasised by the widespread use of drugs targeting this system in clinical practice. These include, renin inhibitors, angiotensin II receptor type I blockers, and inhibitors of the angiotensin converting enzyme. Some of the important effectors within the system are 7 transmembrane (7TM) receptors (or G-protein-coupled receptors) such as the angiotensin II Receptors type I and II (AT1R and AT2R) and the MAS-oncogene receptor. Several findings indicate that the 7TM receptors can form both homo-and heterodimers, or higher orders of oligomers. Furthermore, dimerization may be important for receptor function, and in the development of cardiovascular diseases. This is very significant, since "dimers" may provide pharmacologists with novel targets for improved drug therapy. However, we know that 7TM receptors can mediate signals as monomeric units, and so far it has been very difficult to establish if our observations reflect actual well defined dimerization or merely reflect close proximity between the receptors and/or various types of functional interaction. In this review, we will present and critically discuss the current data on 7TM receptor dimerization with a clear focus on the RAS, and delineate future challenges within the field.

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“…Coffman as previously described (Park et al 2007). Genotyping of mice bred in our colony was performed in duplicate by PCR on DNA obtained by tail biopsy, as previously described (Harrison-Bernard et al 2006;Shen et al 2007;Swafford Jr. et al 2007). Kidneys were obtained from adult male WT (n56), AT 1A 2/2 (n53), AT 1B 2/2 (n53), and AT 1A 2/2 AT 1B 2/2 (n56) mice that were bred in our colony (n59) and obtained from Dr. T.M.…”

Section: Animalsmentioning

confidence: 99%

Augmented Renal Vascular nNOS and Renin Protein Expression in Angiotensin Type 1 Receptor Null Mice

Park

Harrison‐Bernard

2007

J Histochem Cytochem.

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S U M M A R Y The present study was performed to determine the influence of absence of angiotensin type 1A (AT 1A ) and/or AT 1B receptor feedback regulation of kidney neuronal nitric oxide synthase (nNOS) and renin protein expression. Kidneys were harvested from wildtype (WT), AT 1A 2/2 , AT 1B 2/2 , and AT 1A 2/2 AT 1B 2/2 mice and immunostained for nNOS and renin protein localization. AT 1A 2/2 and AT 1A 2/2 AT 1B2/2 kidneys demonstrated an increase in the percentage of glomeruli with nNOS-positive afferent and interlobular arterioles compared with WT mice. Density of vascular nNOS immunostaining was 20-fold higher in kidneys of AT 1A 2/2 and AT 1A 2/2 AT 1B 2/2 compared with WT mice. Density of macula densa nNOS immunostaining was 7-fold higher in AT 1A 2/2 AT 1B 2/2 than in WT mice. Percent of glomeruli positive for juxtaglomerular (JG) cell renin was 3-fold higher, whereas the density of JG cell renin immunostaining was 15-fold higher in kidneys of AT 1A 2/2 and AT 1A 2/2 AT 1B 2/2 compared with WT mice. Kidneys of AT 1A 2/2 and AT 1A 2/2 AT 1B 2/2 mice displayed recruitment of renin protein expression along afferent and interlobular arterioles. Absence of AT 1 receptor signaling resulted in enhanced nNOS protein expression in both microvascular and tubular structures. Enhanced NO generation may contribute to the reduced renal vascular tone and blood pressure observed with blockade of the renin-angiotensin system.

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The Bradykinin B2 Receptor Gene Is a Target of Angiotensin II Type 1 Receptor Signaling

Abstract: Cross-talk between G protein-coupled receptors (GPCR) is known to occur at multiple levels, including receptor heterodimerization and intracellular signaling. This study tested the hypothesis that GPCR cross-talk occurs at the transcriptional level.

Cited by 38 publications

References 40 publications

Histone Deacetylase (HDAC) Activity Is Critical for Embryonic Kidney Gene Expression, Growth, and Differentiation

Histone Deacetylase (HDAC) Activity Is Critical for Embryonic Kidney Gene Expression, Growth, and Differentiation

Functional interactions between 7TM receptors in the Renin-Angiotensin System—Dimerization or crosstalk?

Augmented Renal Vascular nNOS and Renin Protein Expression in Angiotensin Type 1 Receptor Null Mice

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