Potential cross-talk between (pro)renin receptors and Wnt/frizzled receptors in cardiovascular and renal disorders

Balakumar, Pitchai; Jagadeesh, Gowraganahalli

doi:10.1038/hr.2011.113

Cited by 24 publications

(12 citation statements)

References 137 publications

(251 reference statements)

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“…We also could not confirm the predictive value of increased s(P)RR concentration before delivery (in early, middle, and late pregnancy) for preeclampsia in this study. However, as (P)RR contributes to renal disorders, 25 s(P)RR might be associated with proteinuria in preeclampsia pathogenesis, given that high levels of s(P)RR at delivery were associated with the incidence of preeclampsia but not BP late in pregnancy. Future studies are needed to clarify the causal relationship between elevated s(P)RR levels and the pathophysiology of preeclampsia.…”

Section: Discussionmentioning

confidence: 99%

Soluble (Pro)Renin Receptor and Blood Pressure During Pregnancy

et al. 2012

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http://hyper.ahajournals.org/ Downloaded from Watanabe et al S(P)RR During Pregnancy 1251invasion and migration. 16,17 Clinically during pregnancy, it is well-known that even women with no complication exhibit BP changes with gestational age; the BP is typically at its lowest between 24 and 26 gestational weeks, increasing thereafter until the end of the pregnancy. 18 In addition, the circulating RAS is involved in the development of hypertensive disorders, including preeclampsia, during pregnancy. 1,16,19 However, no evidence suggests that the tissue RAS contributes to BP changes during pregnancy.On the basis of these background findings, the present study was conducted to examine whether the tissue RAS contributed to BP changes during pregnancy and the incidence of preeclampsia. To this end, we assessed the relationship between plasma s(P)RR concentrations and BP levels during pregnancy in a prospective cohort study. Methods Study ParticipantsIn this prospective cohort study, Japanese pregnant women whose first visit to the National Center for Child Health and Development hospital was at <16 weeks and 0 days of gestation were enrolled between January and December 2010. At recruitment, written informed consent was obtained from all participants. The study protocol was approved by the ethics committee of the National Center for Child Health and Development (Tokyo, Japan).The expected due date was confirmed by ultrasound in all participants. Inclusion criteria were systolic BP <140 mm Hg and diastolic BP <90 mm Hg at the time of enrollment (<16 weeks of gestation) and the absence of preexisting hypertensive disorders and renal disease. The study initially enrolled 477 pregnant women who met the criteria; however, 40 pregnant women were excluded because of early abortion (n=8) or the inability to follow-up because of relocation (n=32), resulting in a total of 437 study participants.Plasma samples were obtained at 3 prenatal visits throughout the pregnancy and at time of delivery. The first sample was obtained before 16 weeks 0 days gestation (early pregnancy), the second between 16 weeks 0 days and 27 weeks 6 days gestation (mid-pregnancy), and the third after 28 weeks 0 days gestation (late pregnancy) at routine blood testing during prenatal visits. The fourth blood sample was obtained at time of delivery. We determined s(P)RR concentrations for first, second, and third trimester using the blood samples obtained in early, middle, and late pregnancy, respectively. We then analyzed s(P) RR concentrations in early pregnancy in association with BP values measured at 16 to 20, 20 to 24, 24 to 28, 28 to 32, 32 to 36, and 36 to 40 weeks of gestation (6 periods). Similarly, s(P)RR concentrations in mid-pregnancy were analyzed in association with BP levels measured at 28 to 32, 32 to 36, and 36 to 40 weeks gestation (3 periods) and s(P)RR concentrations in late pregnancy with BP levels measured at 36 to 40 weeks gestation (1 period). Finally, s(P)RR at delivery was used for analysis of the association between s(P)RR conce...

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Section: Discussionmentioning

confidence: 99%

Soluble (Pro)Renin Receptor and Blood Pressure During Pregnancy

et al. 2012

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“…WNT3 belongs to the Wnt/frizzled receptor signaling pathway, which has been suggested to have an important functional role in cardiovascular and renal disorders. 40…”

Section: Application To the Bp Gwas Data From The Continental Originsmentioning

confidence: 99%

Meta-analysis of Correlated Traits via Summary Statistics from GWASs with an Application in Hypertension

Zhu

Feng

Tayo

et al. 2015

The American Journal of Human Genetics

314

479

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Genome-wide association studies (GWASs) have identified many genetic variants underlying complex traits. Many detected genetic loci harbor variants that associate with multiple-even distinct-traits. Most current analysis approaches focus on single traits, even though the final results from multiple traits are evaluated together. Such approaches miss the opportunity to systemically integrate the phenome-wide data available for genetic association analysis. In this study, we propose a general approach that can integrate association evidence from summary statistics of multiple traits, either correlated, independent, continuous, or binary traits, which might come from the same or different studies. We allow for trait heterogeneity effects. Population structure and cryptic relatedness can also be controlled. Our simulations suggest that the proposed method has improved statistical power over single-trait analysis in most of the cases we studied. We applied our method to the Continental Origins and Genetic Epidemiology Network (COGENT) African ancestry samples for three blood pressure traits and identified four loci (CHIC2, HOXA-EVX1, IGFBP1/IGFBP3, and CDH17; p < 5.0 × 10(-8)) associated with hypertension-related traits that were missed by a single-trait analysis in the original report. Six additional loci with suggestive association evidence (p < 5.0 × 10(-7)) were also observed, including CACNA1D and WNT3. Our study strongly suggests that analyzing multiple phenotypes can improve statistical power and that such analysis can be executed with the summary statistics from GWASs. Our method also provides a way to study a cross phenotype (CP) association by using summary statistics from GWASs of multiple phenotypes.

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“…The pro-proliferative effect of the prorenin-(P)RR-PLZF axis was previously demonstrated by our group (24) whereas the constitutive functions of the (P)RR were analysed in the present study. MAPKs (78), the Wnt pathway (79) and V-ATPases (80) are known to mediate proliferation in general and likely contribute to pro-survival/pro-proliferative effects of the (P)RR (21,51,81,82). In addition, the phosphatase PRL-1 may be involved in the regulation of proliferation downstream of the (P)RR (1).…”

Section: Figurementioning

confidence: 99%

The (pro)renin receptor mediates constitutive PLZF-independent pro-proliferative effects which are inhibited by bafilomycin but not genistein

Kirsch

Schrezenmeier

Klare

et al. 2014

International Journal of Molecular Medicine

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The (pro)renin receptor [(P)RR] is crucial for cardio-renal pathophysiology. The distinct molecular mechanisms of this receptor are still incompletely understood. The (P)RR is able to interact with different signalling proteins such as promyelocytic leukemia zinc finger protein (PLZF) and Wnt receptors. Moreover, domains of the (P)RR are essential for V-ATPase activity. V-ATPase- and Wnt-mediated effects imply constitutive, i.e., (pro)renin-independent functions of the (P)RR. Regarding ligand-dependent (P)RR signalling, the role of prorenin glycosylation is currently unknown. Therefore, the aim of this study was to analyse the contribution of constitutive (P)RR activity to its cellular effects and the relevance of prorenin glycosylation on its ligand activity. We were able to demonstrate that high glucose induces (P)RR signal transduction whereas deglycosylation of prorenin abolishes its intrinsic activity in neuronal and epithelial cells. By using siRNA against (P)RR or PLZF as well as the PLZF translocation blocker genistein and the specific V-ATPase inhibitor bafilomycin, we were able to dissect three distinct sub-pathways downstream of the (P)RR. The V-ATPase function is ligand-independently associated with strong pro-proliferative effects whereas prorenin causes moderate proliferation in vitro. In contrast, PLZF per se [i.e., in the absence of (pro)renin] does not interfere with cell number.

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Potential cross-talk between (pro)renin receptors and Wnt/frizzled receptors in cardiovascular and renal disorders

Cited by 24 publications

References 137 publications

Soluble (Pro)Renin Receptor and Blood Pressure During Pregnancy

Soluble (Pro)Renin Receptor and Blood Pressure During Pregnancy

Meta-analysis of Correlated Traits via Summary Statistics from GWASs with an Application in Hypertension

The (pro)renin receptor mediates constitutive PLZF-independent pro-proliferative effects which are inhibited by bafilomycin but not genistein

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