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  • 1
    In: Clinical Science, Portland Press Ltd., Vol. 127, No. 8 ( 2014-10-01), p. 539-548
    Abstract: Death-associated protein kinase 3 (DAPK3) also known as zipper-interacting kinase is a serine/threonine kinase that mainly regulates cell death and smooth muscle contraction. We have previously found that protein expression of DAPK3 increases in the mesenteric artery from spontaneously hypertensive rats (SHRs) and that DAPK3 mediates the development of hypertension in SHRs partly through promoting reactive oxygen species-dependent vascular inflammation. However, it remains to be clarified how DAPK3 controls smooth muscle cell (SMC) proliferation and migration, which are also important processes for hypertension development. We, therefore, sought to investigate whether DAPK3 affects SMC proliferation and migration. siRNA against DAPK3 significantly inhibited platelet-derived growth factor (PDGF)-BB-induced SMC proliferation and migration as determined by bromodeoxyuridine (BrdU) incorporation and a cell counting assay as well as a Boyden chamber assay respectively. DAPK3 siRNA or a pharmacological inhibitor of DAPK3 inhibited PDGF-BB-induced lamellipodia formation as determined by rhodamine–phalloidin staining. DAPK3 siRNA or the DAPK inhibitor significantly reduced PDGF-BB-induced activation of p38 and heat-shock protein 27 (HSP27) as determined by Western blotting. In ex vivo studies, PDGF-BB-induced SMC out-growth was significantly inhibited by the DAPK inhibitor. In vivo, the DAPK inhibitor significantly prevented carotid neointimal hyperplasia in a mouse ligation model. The present results, for the first time, revealed that DAPK3 mediates PDGF-BB-induced SMC proliferation and migration through activation of p38/HSP27 signals, which may lead to vascular structural remodelling including neointimal hyperplasia. The present study suggests DAPK3 as a novel pharmaceutical target for the prevention of hypertensive cardiovascular diseases.
    Type of Medium: Online Resource
    ISSN: 0143-5221 , 1470-8736
    Language: English
    Publisher: Portland Press Ltd.
    Publication Date: 2014
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  • 2
    Online Resource
    Online Resource
    Japanese Society of Veterinary Science ; 2021
    In:  Journal of Veterinary Medical Science Vol. 83, No. 1 ( 2021), p. 42-47
    In: Journal of Veterinary Medical Science, Japanese Society of Veterinary Science, Vol. 83, No. 1 ( 2021), p. 42-47
    Type of Medium: Online Resource
    ISSN: 0916-7250 , 1347-7439
    Language: English
    Publisher: Japanese Society of Veterinary Science
    Publication Date: 2021
    detail.hit.zdb_id: 2039077-4
    SSG: 22
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  • 3
    Online Resource
    Online Resource
    IOP Publishing ; 2003
    In:  Japanese Journal of Applied Physics Vol. 42, No. Part 1, No. 4A ( 2003-4-15), p. 1725-1731
    In: Japanese Journal of Applied Physics, IOP Publishing, Vol. 42, No. Part 1, No. 4A ( 2003-4-15), p. 1725-1731
    Type of Medium: Online Resource
    ISSN: 0021-4922 , 1347-4065
    RVK:
    RVK:
    RVK:
    Language: English
    Publisher: IOP Publishing
    Publication Date: 2003
    detail.hit.zdb_id: 218223-3
    detail.hit.zdb_id: 797294-5
    detail.hit.zdb_id: 2006801-3
    detail.hit.zdb_id: 797295-7
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  • 4
    In: Japanese Journal of Applied Physics, IOP Publishing, Vol. 55, No. 1S ( 2016-01-01), p. 01AA18-
    Abstract: The process controllability of inductively coupled plasma-enhanced reactive sputter deposition for the fabrication of amorphous InGaZnO x (a-IGZO) channel thin-film transistors (TFTs) was investigated. a-IGZO film deposition with the addition of H 2 gas was performed using a plasma-assisted reactive sputtering system to control the oxidation process during a-IGZO film formation by balancing the oxidation and reduction reactions. Optical emission spectroscopy measurements indicate the possibility for the oxidation reaction to be inhibited by a decrease in the density of oxygen atoms and the reduction effect of hydrogen during a-IGZO film deposition due to the addition of H 2 gas. The characteristics of TFTs fabricated using a-IGZO films deposited with a plasma-enhanced magnetron sputtering deposition system were investigated. The results indicate the possibility of expanding the process window by controlling the balance between oxidation and reduction with the addition of H 2 gas. TFTs with a-IGZO films that were deposited with the addition of H 2 gas exhibited good performance with a field-effect mobility (μ FE ) of 15.3 cm 2 V −1 s −1 and a subthreshold gate voltage swing ( S ) of 0.48 V decade −1 .
    Type of Medium: Online Resource
    ISSN: 0021-4922 , 1347-4065
    RVK:
    RVK:
    RVK:
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2016
    detail.hit.zdb_id: 218223-3
    detail.hit.zdb_id: 797294-5
    detail.hit.zdb_id: 2006801-3
    detail.hit.zdb_id: 797295-7
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  • 5
    Online Resource
    Online Resource
    Japanese Society of Veterinary Science ; 2022
    In:  Journal of Veterinary Medical Science Vol. 84, No. 10 ( 2022), p. 1352-1357
    In: Journal of Veterinary Medical Science, Japanese Society of Veterinary Science, Vol. 84, No. 10 ( 2022), p. 1352-1357
    Type of Medium: Online Resource
    ISSN: 0916-7250 , 1347-7439
    Language: English
    Publisher: Japanese Society of Veterinary Science
    Publication Date: 2022
    detail.hit.zdb_id: 2039077-4
    SSG: 22
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  • 6
    Online Resource
    Online Resource
    Japanese Society of Veterinary Science ; 2017
    In:  Journal of Veterinary Medical Science Vol. 79, No. 9 ( 2017), p. 1516-1523
    In: Journal of Veterinary Medical Science, Japanese Society of Veterinary Science, Vol. 79, No. 9 ( 2017), p. 1516-1523
    Type of Medium: Online Resource
    ISSN: 0916-7250 , 1347-7439
    Language: English
    Publisher: Japanese Society of Veterinary Science
    Publication Date: 2017
    detail.hit.zdb_id: 2039077-4
    SSG: 22
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  • 7
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 21 ( 2021-10-30), p. 11812-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 21 ( 2021-10-30), p. 11812-
    Abstract: Adipocytokine chemerin is a biologically active molecule secreted from adipose tissue. Chemerin elicits a variety of functions via chemokine-like receptor 1 (CMKLR1). The cardiovascular center in brain that regulates blood pressure (BP) is involved in pathophysiology of systemic hypertension. Thus, we explored the roles of brain chemerin/CMKLR1 on regulation of BP in spontaneously hypertensive rats (SHR). For this aim, we examined effects of intracerebroventricular (i.c.v.) injection of CMKLR1 small interfering (si)RNA on both systemic BP as measured by tail cuff system and protein expression in paraventricular nucleus (PVN) of SHR as determined by Western blotting. We also examined both central and peripheral protein expression of chemerin by Western blotting. Systolic BP of SHR but not normotensive Wistar Kyoto rats (WKY) was decreased by CMKLR1 siRNA. The decrease of BP by CMKLR1 siRNA persisted for 3 days. Protein expression of CMKLR1 in PVN of SHR tended to be increased compared with WKY, which was suppressed by CMKLR1 siRNA. Protein expression of chemerin in brain, peripheral plasma, and adipose tissue was not different between WKY and SHR. In summary, we for the first time revealed that the increased protein expression of CMKLR1 in PVN is at least partly responsible for systemic hypertension in SHR.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 8 ( 2022-04-11), p. 4228-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 8 ( 2022-04-11), p. 4228-
    Abstract: Zucker fatty diabetes mellitus (ZFDM) rats harboring the missense mutation (fa) in a leptin receptor gene have been recently established as a novel animal model of obesity and type 2 diabetes (T2D). Here, we explored changes in cardiovascular dynamics including blood pressure and heart rate (HR) associated with the progression of obesity and T2D, as well as pathological changes in adipose tissue and kidney. There was no significant difference in systolic blood pressure (SBP) in ZFDM-Leprfa/fa (Homo) compared with ZFDM-Leprfa/+ (Hetero) rats, while HR and plasma adrenaline in Homo were significantly lower than Hetero. The mRNA expression of monocyte chemotactic protein-1 in perirenal white adipose tissue (WAT) from Homo was significantly higher than Hetero. Interscapular brown adipose tissue (BAT) in Homo was degenerated and whitened. The plasma blood urea nitrogen in Homo was significantly higher than Hetero. In summary, we demonstrated for the first time that HR and plasma adrenaline concentration but not SBP in Homo decrease with obesity and T2D. In addition, inflammation occurs in WAT from Homo, while whitening occurs in BAT. Further, renal function is impaired in Homo. In the future, ZFDM rats will be useful for investigating metabolic changes associated with the progression of obesity and T2D.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    MDPI AG ; 2019
    In:  International Journal of Molecular Sciences Vol. 20, No. 19 ( 2019-09-26), p. 4780-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 20, No. 19 ( 2019-09-26), p. 4780-
    Abstract: Small extracellular vesicles (sEVs) mediate cell–to–cell communication. We recently reported that circulating sEVs regulate systolic blood pressure in an animal model of human systemic hypertension. However, the underlying mechanisms still remain to be elucidated. As the first step for detailed analyses, we sought to increase the yield and purity of sEVs isolated from rat plasma. We compared the concentration and size distribution of sEVs as well as protein expression of the sEV marker and contaminants among plasma sEVs isolated by the ultracentrifugation (UC) method, the precipitation with polyethylene-glycol and ultracentrifugation (PEG-UC) method, or the precipitation with polyethylene-glycol (PEG) method. Effects of anticoagulants were also examined. The total concentration of plasma sEVs isolated by the PEG or PEG-UC method was much higher than that of the UC method. In the plasma sEVs isolated by the PEG-UC method, contaminating proteins were lower, while the protein expression of certain sEV markers was higher than that of the PEG method. There was no significant difference in total concentration or protein expression of sEV markers in sEVs isolated from rat plasma treated with three different anticoagulants (heparin, ethylenediaminetetraacetic acid, or acid citrate dextrose buffer) by the PEG-UC method. We, for the first time, determined that the PEG-UC method was optimal for sEV isolation from rat plasma.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 10
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2019-11-14)
    Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) cause damage in the small intestine in a bacteria-dependent manner. As high-fat diet (HFD) is a potent inducer of gut dysbiosis, we investigated the effects of HFD on bacterial flora in the small intestine and NSAID-induced enteropathy. 16S rRNA gene analysis revealed that the population of Bifidobacterium spp. significantly decreased by fold change of individual operational taxonomic units in the small intestine of mice fed HFD for 8 weeks. HFD increased intestinal permeability, as indicated by fluorescein isothiocyanate-dextran absorption and serum lipopolysaccharide levels, accompanied by a decrease in the protein expressions of ZO-1 and occludin and elevated mRNA expression of interleukin (IL)-17A in the small intestine. HFD-fed mice exhibited increased susceptibility to indomethacin-induced damage in the small intestine; this phenotype was observed in normal diet-fed mice that received small intestinal microbiota from HFD-fed mice. Administration of neutralizing antibodies against IL-17A to HFD-fed mice reduced intestinal permeability and prevented exacerbation of indomethacin-induced damage. Thus, HFD-induced microbial dysbiosis in small intestine caused microinflammation through the induction of IL-17A and increase in intestinal permeability, resulting in the aggravation of NSAID-induced small intestinal damage.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2615211-3
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