Exclusion of the Catechol-O-Methyltransferase Gene from Genes Contributing to Salt-Sensitive Hypertension in Dahl Salt-Sensitive Rats

Kajimoto, Kazuaki; Hiura, Yumiko; Sumiya, Toshiki; Yasui, Naomi; Okuda, Tomohiko; Iwai, Naoharu

doi:10.1291/hypres.30.459

Cited by 9 publications

(8 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The protein concentrations in cell lysates were determined with a BCA Protein Assay Kit (Pierce, Rockford, IL, USA). The cell lysates were subjected to immunodetection, as described previously [55]. The antibodies utilized in this study are listed in Table S2.…”

Section: Methodsmentioning

confidence: 99%

Cytoprotective role of the fatty acid binding protein 4 against oxidative and endoplasmic reticulum stress in 3T3‐L1 adipocytes

2014

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Methodsmentioning

confidence: 99%

Cytoprotective role of the fatty acid binding protein 4 against oxidative and endoplasmic reticulum stress in 3T3‐L1 adipocytes

2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is also reported that P2X 7 genetic variation significantly affects blood pressure in a Caucasian population (19). Although the pathophysiology of hypertension and renal diseases is well studied (14,31), few studies address the role of the P2X 7 receptor in the progression of hypertension and renal diseases. Therefore, the relevance of the P2X 7 receptor in hypertension and renal injury remains to be elucidated.…”

mentioning

confidence: 99%

P2X₇ deficiency attenuates hypertension and renal injury in deoxycorticosterone acetate-salt hypertension

Naito

Weng

et al. 2012

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

The P2X(7) receptor is a ligand-gated ion channel, and genetic variations in the P2X(7) gene significantly affect blood pressure. P2X(7) receptor expression is associated with renal injury and inflammatory diseases. Uninephrectomized wild-type (WT) and P2X(7)-deficient (P2X(7) KO) mice were subcutaneously implanted with deoxycorticosterone acetate (DOCA) pellets and fed an 8% salt diet for 18 days. Their blood pressure was assessed by a telemetry system. The mice were placed in metabolic cages, and urine was collected for 24 h to assess renal function. After 18 days of DOCA-salt treatment, P2X(7) mRNA and protein expression increased in WT mice. Blood pressure in P2X(7) KO mice was less than that of WT mice (mean systolic blood pressure 133 ± 3 vs. 150 ± 2 mmHg). On day 18, urinary albumin excretion was lower in P2X(7) KO mice than in WT mice (0.11 ± 0.07 vs. 0.28 ± 0.07 mg/day). Creatinine clearance was higher in P2X(7) KO mice than in WT mice (551.53 ± 65.23 vs. 390.85 ± 32.81 μl·min(-1)·g renal weight(-1)). Moreover, renal interstitial fibrosis and infiltration of immune cells (macrophages, T cells, B cells, and leukocytes) were markedly attenuated in P2X(7) KO mice compared with WT mice. The levels of IL-1β, released by macrophages, in P2X(7) KO mice had decreased dramatically compared with that in WT mice. These results strongly suggest that the P2X(7) receptor plays a key role in the development of hypertension and renal disease via increased inflammation, indicating its potential as a novel therapeutic target.

show abstract

“…Others report from one to three sequentially applied criteria to select lists of differentially expressed genes, which varied in nature and in statistical support. For instance, arbitrary thresholds by absolute intensity difference or fold changes (FC) [27-33], different combinations of FC and t -statistics [34-36], ranking by FC and selecting only the top 100 most significant genes [37], correlation to a hypothetical constant gene [38], and concordance in FC direction across experimental groups [39], among others (for the complete list studies with details about experimental design, see Additional file 1). Although applying multiple criteria can be attractive in terms of reducing the number of candidates, this is likely to reduce power in an unpredictable manner.…”

Section: Resultsmentioning

confidence: 99%

“…A total of nine studies were identified that compared gene expression between rat strains that showed spontaneous difference for blood pressure [31-33,40,41] or between congenic and background strains created from these lines [30,42-44]. These studies have led to the direct identification of as many as 50 candidate genes for hypertension and to the confirmation of at least one causal gene, namely, Klk1 [31].…”

Section: Resultsmentioning

confidence: 99%

Serious limitations of the QTL/Microarray approach for QTL gene discovery

et al. 2010

View full text Add to dashboard Cite

BackgroundIt has been proposed that the use of gene expression microarrays in nonrecombinant parental or congenic strains can accelerate the process of isolating individual genes underlying quantitative trait loci (QTL). However, the effectiveness of this approach has not been assessed.ResultsThirty-seven studies that have implemented the QTL/microarray approach in rodents were reviewed. About 30% of studies showed enrichment for QTL candidates, mostly in comparisons between congenic and background strains. Three studies led to the identification of an underlying QTL gene. To complement the literature results, a microarray experiment was performed using three mouse congenic strains isolating the effects of at least 25 biometric QTL. Results show that genes in the congenic donor regions were preferentially selected. However, within donor regions, the distribution of differentially expressed genes was homogeneous once gene density was accounted for. Genes within identical-by-descent (IBD) regions were less likely to be differentially expressed in chromosome 2, but not in chromosomes 11 and 17. Furthermore, expression of QTL regulated in cis (cis eQTL) showed higher expression in the background genotype, which was partially explained by the presence of single nucleotide polymorphisms (SNP).ConclusionsThe literature shows limited successes from the QTL/microarray approach to identify QTL genes. Our own results from microarray profiling of three congenic strains revealed a strong tendency to select cis-eQTL over trans-eQTL. IBD regions had little effect on rate of differential expression, and we provide several reasons why IBD should not be used to discard eQTL candidates. In addition, mismatch probes produced false cis-eQTL that could not be completely removed with the current strains genotypes and low probe density microarrays. The reviewed studies did not account for lack of coverage from the platforms used and therefore removed genes that were not tested. Together, our results explain the tendency to report QTL candidates as differentially expressed and indicate that the utility of the QTL/microarray as currently implemented is limited. Alternatives are proposed that make use of microarray data from multiple experiments to overcome the outlined limitations.

show abstract

Exclusion of the Catechol-O-Methyltransferase Gene from Genes Contributing to Salt-Sensitive Hypertension in Dahl Salt-Sensitive Rats

Cited by 9 publications

References 24 publications

Cytoprotective role of the fatty acid binding protein 4 against oxidative and endoplasmic reticulum stress in 3T3‐L1 adipocytes

Cytoprotective role of the fatty acid binding protein 4 against oxidative and endoplasmic reticulum stress in 3T3‐L1 adipocytes

P2X₇ deficiency attenuates hypertension and renal injury in deoxycorticosterone acetate-salt hypertension

Serious limitations of the QTL/Microarray approach for QTL gene discovery

Contact Info

Product

Resources

About

Exclusion of the Catechol-O-Methyltransferase Gene from Genes Contributing to Salt-Sensitive Hypertension in Dahl Salt-Sensitive Rats

Cited by 9 publications

References 24 publications

Cytoprotective role of the fatty acid binding protein 4 against oxidative and endoplasmic reticulum stress in 3T3‐L1 adipocytes

Cytoprotective role of the fatty acid binding protein 4 against oxidative and endoplasmic reticulum stress in 3T3‐L1 adipocytes

P2X7 deficiency attenuates hypertension and renal injury in deoxycorticosterone acetate-salt hypertension

Serious limitations of the QTL/Microarray approach for QTL gene discovery

Contact Info

Product

Resources

About

P2X₇ deficiency attenuates hypertension and renal injury in deoxycorticosterone acetate-salt hypertension