ASK3 responds to osmotic stress and regulates blood pressure by suppressing WNK1-SPAK/OSR1 signaling in the kidney

Naguro, Isao; Umeda, Tomohiro; Kobayashi, Y.; Maruyama, Junichi; Hattori, Kazuki; Shimizu, Yutaka; Kataoka, Kazunori; Kim‐Mitsuyama, Shokei; Uchida, Shinichi; Vandewalle, Alain; Noguchi, Takuya; Nishitoh, Hideki; Matsuzawa, Atsushi; Takeda, Kohsuke; Ichijo, Hidenori

doi:10.1038/ncomms2283

Cited by 70 publications

(98 citation statements)

References 40 publications

(83 reference statements)

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“…oxidative stress) was induced during sternotomy using diathermy46. In addition to this finding, our data revealed that sternotomy affected the levels of antioxidants (inosine, hypoxanthine) and metabolites involved in oxidative stress (trigonelline47), cell-volume regulation (glycine4849), and tissue damage (3-methylhistidine50) (Fig. 6).…”

Section: Discussionsupporting

confidence: 65%

Metabotyping Patients’ Journeys Reveals Early Predisposition to Lung Injury after Cardiac Surgery

Maltesen

Rasmussen

Pedersen

et al. 2017

Sci Rep

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Cardiovascular disease is the leading cause of death worldwide and patients with severe symptoms undergo cardiac surgery. Even after uncomplicated surgeries, some patients experience postoperative complications such as lung injury. We hypothesized that the procedure elicits metabolic activity that can be related to the disease progression, which is commonly observed two-three days postoperatively. More than 700 blood samples were collected from 50 patients at nine time points pre-, intra-, and postoperatively. Dramatic metabolite shifts were observed during and immediately after the intervention. Prolonged surgical stress was linked to an augmented anaerobic environment. Time series analysis showed shifts in purine-, nicotinic acid-, tyrosine-, hyaluronic acid-, ketone-, fatty acid, and lipid metabolism. A characteristic ‘metabolic biosignature’ was identified correlating with the risk of developing postoperative complications two days before the first clinical signs of lung injury. Hence, this study demonstrates the link between intra- and postoperative time-dependent metabolite changes and later postoperative outcome. In addition, the results indicate that metabotyping patients’ journeys early, during or just after the end of surgery, may have potential impact in hospitals for the early diagnosis of postoperative lung injury, and for the monitoring of therapeutics targeting disease progression.

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Section: Discussionsupporting

confidence: 65%

Metabotyping Patients’ Journeys Reveals Early Predisposition to Lung Injury after Cardiac Surgery

Maltesen

Rasmussen

Pedersen

et al. 2017

Sci Rep

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“…Loss-offunction alleles of Coco and Bic-C cause similar defects in organ positioning, raising the possibility that Bic-C may control Coco in somatic cells. Similarly, multiple other targets of Bic-C identified here (e.g., the mRNAs encoding the Wnk1 and VATPase B1 proteins) are critical for normal kidney development and function (Karet et al 1999a,b;Arroyo and Gamba 2012;Naguro et al 2012). Thus, our findings and the recent demonstration that adenylate cyclase6 mRNA is a Bic-C target in kidney cells (Piazzon et al 2012) support the idea that translational control by Bic-C plays a key role in renal development and point to relevant mRNA targets worth further inquiry.…”

Section: Discussionmentioning

confidence: 79%

Bicaudal-C spatially controls translation of vertebrate maternal mRNAs

Zhang

Cooke

Park

et al. 2013

RNA

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The Xenopus Cripto-1 protein is confined to the cells of the animal hemisphere during early embryogenesis where it regulates the formation of anterior structures. Cripto-1 protein accumulates only in animal cells because cripto-1 mRNA in cells of the vegetal hemisphere is translationally repressed. Here, we show that the RNA binding protein, Bicaudal-C (Bic-C), functioned directly in this vegetal cell-specific repression. While Bic-C protein is normally confined to vegetal cells, ectopic expression of Bic-C in animal cells repressed a cripto-1 mRNA reporter and associated with endogenous cripto-1 mRNA. Repression by Bic-C required its N-terminal domain, comprised of multiple KH motifs, for specific binding to relevant control elements within the cripto-1 mRNA and a functionally separable C-terminal translation repression domain. Bic-C-mediated repression required the 5 ′ CAP and translation initiation factors, but not a poly(A) tail or the conserved SAM domain within Bic-C. Bic-C-directed immunoprecipitation followed by deep sequencing of associated mRNAs identified multiple Bic-C-regulated mRNA targets, including cripto-1 mRNA, providing new insights and tools for understanding the role of Bic-C in vertebrate development.

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“…The molecular function of MAP3K15 in stickleback is unknown, but we assumed that it is the same as it is in mammalian kidneys. Recently, Naguro et al (2012) found that MAP3K15 is expressed in the epithelium of the renal tubules in mouse kidney. They monitored the kinase activity of endogenous MAP3K15 in human HEK293A cells after gradually altering the concentration of NaCl by 10–mM steps or mannitol by 20–mM steps in extracellular solutions.…”

Section: Resultsmentioning

confidence: 99%

“…They also found that knockdown of MAP3K15 , by short interfering RNA, enhanced the activation of the WNK1-SPAK/OSR1 signaling pathway. Moreover, MAP3K15 KO mice exhibited a hypertensive phenotype: the systolic BP of KO mice increased significantly along with aging (Naguro et al, 2012). …”

Section: Resultsmentioning

confidence: 99%

Gene expression responses of threespine stickleback to salinity: implications for salt-sensitive hypertension

et al. 2014

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Despite recent success with genome-wide association studies (GWAS), identifying hypertension (HTN)-susceptibility loci in the general population remains difficult. Here, we present a novel strategy to address this challenge by studying salinity adaptation in the threespine stickleback, a fish species with diverse salt-handling ecotypes. We acclimated native freshwater (FW) and anadromous saltwater (SW) threespine sticklebacks to fresh, brackish, and sea water for 30 days, and applied RNA sequencing to determine the gene expression in fish kidneys. We identified 1844 salt-responsive genes that were differentially expressed between FW sticklebacks acclimated to different salinities and/or between SW and FW sticklebacks acclimated to full-strength sea water. Significant overlap between stickleback salt-responsive genes and human genes implicated in HTN was detected (P < 10−7, hypergeometric test), suggesting a possible similarity in genetic mechanisms of salt handling between threespine sticklebacks and humans. The overlapping genes included a newly discovered HTN gene—MAP3K15, whose expression in FW stickleback kidneys decreases with salinity. These also included genes located in the GWAS loci such as AGTRAP-PLOD1 and CYP1A1-ULK3, which contain multiple potentially causative genes contributing to HTN susceptibility that need to be prioritized for study. Taken together, we show that stickleback salt-responsive genes provide valuable information facilitating the identification of human HTN genes. Thus, threespine sticklebacks may be used as a model, complementary to existing animal models, in human HTN research.

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ASK3 responds to osmotic stress and regulates blood pressure by suppressing WNK1-SPAK/OSR1 signaling in the kidney

Cited by 70 publications

References 40 publications

Metabotyping Patients’ Journeys Reveals Early Predisposition to Lung Injury after Cardiac Surgery

Metabotyping Patients’ Journeys Reveals Early Predisposition to Lung Injury after Cardiac Surgery

Bicaudal-C spatially controls translation of vertebrate maternal mRNAs

Gene expression responses of threespine stickleback to salinity: implications for salt-sensitive hypertension

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