Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Nakaya Michio Last modified date:2022.06.27

Associate Professor / Department of Disease Control / Department of Pharmaceutical Health Care and Sciences / Faculty of Pharmaceutical Sciences

1. Kotaro Kasai, Yuma Horii, Takanori Hironaka, Kyosuke Mae, Tomoyuki Ueno, Akiomi Nagasaka, and Michio Nakaya*, Increased Expression of Heparan Sulfate 6-O-sulfotransferase-2 Promotes Collagen Production in Cardiac Myofibroblasts., BPB report., 4, 85, 91, 2021.05.
2. Noburo Takizawa, Takanori Hironaka, Kyosuke Mae, Tomoyuki Ueno, Yuma Horii, Akiomi Nagasaka, and Michio Nakaya, GPRC5B promotes collagen production in myofibroblasts., Biochem. Biophys. Res. Commun., 561, 180, 186, 2021.05.
3. Yuya Yoshida, Naoya Matsunaga, Takaharu Nakao, Kengo Hamamura, Hideaki Kondo, Tomomi Ide, Hiroyuki Tsutsui, Akito Tsuruta, Masayuki Kurogi, and Michio Nakaya, Hitoshi Kurose, Satoru Koyanagi, and Shigehiro Ohdo, Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis., Nat. Commun., 12, 1, 2783, 2021.05.
4. Chikashi Yoshimura, Akiomi Nagasaka, Hitoshi Kurose, & Michio Nakaya, Efferocytosis during myocardial infarction., Journal of Biochemistry, 2020.08.
5. Takanori Hironaka, Tomoyuki Ueno, Kyosuke Mae, Chikashi Yoshimura, Takumi Morinaga, Yuma Horii, Akiomi Nagasaka, Hitoshi Kurose, Michio Nakaya, Drebrin is induced during myofibroblast differentiation and enhances the production of fibrosis-related genes, Biochemical and Biophysical Research Communications, 10.1016/j.bbrc.2020.05.110, 529, 2, 224-230, 2020.08, Fibrosis is attributed to excess deposition of extracellular matrix (ECM) proteins including collagen and is associated with various organ dysfunction. This excessive ECM is produced by myofibroblasts, which are differentiated from various cells by a variety of stimuli, represented by TGF-β. However, molecular mechanisms for the regulation of ECM production in myofibroblasts remain obscure. In this study, we demonstrate that the expression of drebrin, which binds to and increases the stability of actin filament in neurons, is increased in mouse hearts and lungs upon fibrosis. Drebrin is mainly expressed in myofibroblasts in the fibrotic hearts and lungs and promotes the expression of fibrosis-related genes, such as Acta2 and Col1a1. Taken together, our study identifies drebrin as a molecule that promotes the production of fibrosis-related genes in myofibroblasts..
6. Yuma Horii, Michio Nakaya, Hiroki Ohara, Hiroaki Nishihara, Kenji Watari, Akiomi Nagasaka, Takeo Nakaya, Yuki Sugiura, Toshiaki Okuno, Tomoaki Koga, Akira Tanaka, Takehiko Yokomizo, Hitoshi Kurose, Leukotriene B4 receptor 1 exacerbates inflammation following myocardial infarction, FASEB Journal, 10.1096/fj.202000041R, 34, 6, 8749-8763, 2020.06, Leukotriene B4 receptor 1 (BLT1), a high-affinity G-protein-coupled receptor for leukotriene B4 (LTB4), is expressed on various inflammatory cells and plays critical roles in several inflammatory diseases. In myocardial infarction (MI), various inflammatory cells are known to be recruited to the infarcted area, but the function of BLT1 in MI is poorly understood. Here, we investigated the role of BLT1 in MI and the therapeutic effect of a BLT1 antagonist, ONO-4057, on MI. Mice with infarcted hearts showed increased BLT1 expression and LTB4 levels. BLT1-knockout mice with infarcted hearts exhibited attenuated leukocyte infiltration, proinflammatory cytokine production, and cell death, which led to reduced mortality and improved cardiac function after MI. Bone-marrow transplantation studies showed that BLT1 expressed on bone marrow-derived cells was responsible for the exacerbation of inflammation in infarcted hearts. Furthermore, ONO-4057 administration attenuated the inflammatory responses in hearts surgically treated for MI, which resulted in reduced mortality and improved cardiac function after MI. Our study demonstrated that BLT1 contributes to excessive inflammation after MI and could represent a new therapeutic target for MI..
7. Takeo Nakaya, Masaya Sogabe, Shin-ichi Yamamoto, Kentaro Tsuji, Michio Nakaya, Toshiro Niki, Shunsuke Endo, and Akira Tanaka, Pancreatic carcinoma metastasis to a lung carcinoma lesion and pulmonary fibrotic regions, overtaking the stromal microenvironment, Medicine., doi: 10.1097/MD.0000000000015888., 2019.08.
8. Takeo Nakaya, Masaya Sogabe, Shin Ichi Yamamoto, Kentaro Tsuji, Michio Nakaya, Toshiro Niki, Shunsuke Endo, Akira Tanaka, Pancreatic carcinoma metastasis to a lung carcinoma lesion and pulmonary fibrotic regions, overtaking the stromal microenvironment
A case report, Medicine (United States), 10.1097/MD.0000000000015888, 98, 24, 2019.06, Rationale:Suppression and of cancer metastasis is one of the most important issues in cancer care. Considering the typical clinical course of metastases, cancer cells might prefer certain environments or conditions. However, favorable environments for cancer metastasis have not been clearly identified. We had previously described a case of dual, yet separate, pancreatic and colon cancer, in which the metastatic pancreatic cancer was localized at the invasive portion of the colon cancer. We hypothesized that metastatic pancreatic cancer took over the colon cancer microenvironment.Patient concerns:We experienced an another case of double cancer in a 65-year-old man who had lung squamous cell carcinoma and an independent pancreatic adenocarcinoma that metastasized to the liver as well as to the lung cancer lesion and pulmonary fibrotic regions associated with pneumothorax and bronchiolization.Interventions:The pneumothorax could not be controlled by conservative treatment. Thus, an emergency surgery with partial resection of the lower lobe of right lung was performed.Diagnoses:We found multiple pancreatic cancer metastases in the lung cancer and fibrotic lesions in the surgical specimen. However, we detected no metastasis in normal lung tissues except inside small arteries, although the lung cancer and fibrotic tissue areas were smaller than the normal lung tissue areas in the surgical specimen.Outcomes:The patient died 50 days after the surgery.Lessons:This case may thus provide evidence to strengthen our hypothesis that pancreatic cancer prefers to metastasize to other independent cancer lesions, overtaking the cancer microenvironment constructed by other independent cancers. The lung cancer microenvironment, rich in myofibroblasts and/or cancer-associated fibroblasts, might be suitable for pancreatic carcinoma metastasis. In addition, we propose the hypothesis that compared with normal tissues, noncancerous fibrotic lesions are preferable destinations for cancer metastasis. Furthermore, metastasis of pancreatic carcinoma to lung cancer and fibrotic tissues might be more common, although such cases have not been previously reported..
9. Takanori Hironaka, Yuweki Ohba, Hitoshi Kurose, Michio Nakaya, The roles of inhibitory smads in cancer progression, Folia Pharmacologica Japonica, 10.1254/fpj.154.44, 154, 1, 2019.01.
10. Takashi Iezaki, Kazuya Fukasawa, Tetsuhiro Horie, Gyujin Park, Samuel Robinson, Nakaya Michio, Hiroyuki Fujita, Yuki Onishi, Kakeru Ozaki, Takashi Kanayama, Manami Hiraiwa, Yuka Kitaguchi, Katsuyuki Kaneda, Yukio Yoneda, Takeshi Takarada, X. Edward Guo, Hitoshi Kurose, Eiichi Hinoi, The MAPK Erk5 is necessary for proper skeletogenesis involving a smurf-smad-Sox9 molecular axis, Development (Cambridge), 10.1242/dev.164004, 145, 14, 2018.07, Erk5 belongs to the mitogen-activated protein kinase (MAPK) family. Following its phosphorylation by Mek5, Erk5 modulates several signaling pathways in a number of cell types. In this study, we demonstrated that Erk5 inactivation in mesenchymal cells causes abnormalities in skeletal development by inducing Sox9, an important transcription factor of skeletogenesis. We further demonstrate that Erk5 directly phosphorylates and activates Smurf2 (a ubiquitin E3 ligase) at Thr249, which promotes the proteasomal degradation of Smad proteins and phosphorylates Smad1 at Ser206 in the linker region known to trigger its proteasomal degradation by Smurf1. Smads transcriptionally activated the expression of Sox9 in mesenchymal cells. Accordingly, removal of one Sox9 allele in mesenchymal cells fromErk5-deficient mice rescued some abnormalities of skeletogenesis. These findings highlight the importance of the Mek5-Erk5-Smurf-Smad-Sox9 axis in mammalian skeletogenesis..
11. Taka aki Koshimizu, Kenji Honda, Sachi Nagaoka-Uozumi, Atsuhiko Ichimura, Ikuo Kimura, Nakaya Michio, Nobuya Sakai, Katsushi Shibata, Kentarou Ushijima, Akio Fujimura, Akira Hirasawa, Hitoshi Kurose, Gozoh Tsujimoto, Akito Tanoue, Yukio Takano, Complex formation between the vasopressin 1b receptor, β-arrestin-2, and the μ-opioid receptor underlies morphine tolerance, Nature Neuroscience, 10.1038/s41593-018-0144-y, 1-14, 2018.04, Chronic morphine exposure upregulates adenylate cyclase signaling and reduces analgesic efficacy, a condition known as opioid tolerance. Nonopioid neurotransmitters can enhance morphine tolerance, but the mechanism for this is poorly understood. We show that morphine tolerance was delayed in mice lacking vasopressin 1b receptors (V1bRs) or after administration of V1bR antagonist into the rostral ventromedial medulla, where transcripts for V1bRs and μ-opioid receptors are co-localized. Vasopressin increased morphine-binding affinity in cells expressing both V1bR and μ-opioid receptors. Complex formation among V1bR, β-arrestin-2, and μ-opioid receptor resulted in vasopressin-mediated upregulation of ERK phosphorylation and adenylate cyclase sensitization. A leucine-rich segment in the V1bR C-terminus was necessary for the association with β-arrestin-2. Deletion of this leucine-rich segment increased morphine analgesia and reduced vasopressin-mediated adenylate cyclase sensitization. These findings indicate that inhibition of μ-opioid-receptor-associated V1bR provides an approach for enhancing morphine analgesia without increasing analgesic tolerance..
12. Akiomi Nagasaka, Chihiro Mogi, Hiroki Ono, Toshihide Nishi, Yuma Horii, Yuki Ohba, Koichi Sato, Michio Nakaya, Fumikazu Okajima, Hitoshi Kurose, The proton-sensing G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) shows cardioprotective effects against myocardial infarction, Scientific reports, 10.1038/s41598-017-07573-2, 7, 1, 2017.12, Myocardial infarction (MI) is an ischaemic heart condition caused by the occlusion of coronary arteries. Following MI, lactic acid from anaerobic glycolysis increases and infiltrating immune cells produce severe inflammation, which leads to acidosis in the ischaemic heart. However, the physiological implication of this pH reduction remains largely unknown. T-cell death-associated gene 8 (TDAG8) is a proton-sensing G protein-coupled receptor found on cardiac macrophages that recognise increases in extracellular protons. We demonstrated that TDAG8 negatively regulates the transcription of the chemokine Ccl20. The infarcted hearts of TDAG8 KO mice showed an increase in CCL20 expression and the number of infiltrating IL-17A-producing γδT cells that express CCR6, a receptor for CCL20. Accordingly, excessive IL-17A production, which is linked to the functional deterioration after MI, was observed in MI-operated TDAG8 KO mice. The survival rate and cardiac function significantly decreased in TDAG8 KO mice compared with those in wild-type mice after MI. Thus, our results suggest that TDAG8 is a key regulator of MI and a potential therapeutic target..
13. Gentaro Iribe, Keiko Kaihara, Yohei Yamaguchi, Nakaya Michio, Ryuji Inoue, Keiji Naruse, Mechano-sensitivity of mitochondrial function in mouse cardiac myocytes, Progress in Biophysics and Molecular Biology, 10.1016/j.pbiomolbio.2017.05.015, 130, 315-322, 2017.11, Mitochondria are an important source of reactive oxygen species (ROS). Although it has been reported that myocardial stretch increases cellular ROS production by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), referred to as X-ROS signalling, the involvement of mitochondria in X-ROS is not clear. Mitochondria are organelles that generate adenosine triphosphate (ATP) for cellular energy needs, which are mechanical-load-dependent. Therefore, it would not be surprising if these organelles had mechano-sensitive functions associated with stretch-induced ROS production. In the present study, we investigated the relation between X-ROS and mitochondrial stretch-sensitive responses in isolated mouse cardiac myocytes. The cells were subjected to 10% axial stretch using computer-controlled, piezo-manipulated carbon fibres attached to both cell ends. Cellular ROS production and mitochondrial membrane potential (Δψm) were assessed optically by confocal microscopy. The axial stretch increased ROS production and hyperpolarised Δψm. Treatment with a mitochondrial metabolic uncoupler, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), at 0.5 μM did not suppress stretch-induced ROS production, whereas treatment with a respiratory Complex III inhibitor, antimycin A (5 μM), blunted the response. Although NOX inhibition by apocynin abrogated the stretch-induced ROS production, it did not suppress stretch-induced hyperpolarisation of Δψm. These results suggest that stretch causes activation of the respiratory chain to hyperpolarise Δψm, followed by NOX activation, which increases ROS production..
14. Yaopeng Hu, Yubin Duan, Ayako Takeuchi, Lin Hai-Kurahara, Jun Ichikawa, Keizo Hiraishi, Tomohiro Numata, Hiroki Ohara, Gentaro Iribe, Nakaya Michio, Masayuki X. Mori, Satoshi Matsuoka, Genshan Ma, Ryuji Inoue, Uncovering the arrhythmogenic potential of TRPM4 activation in atrial-derived HL-1 cells using novel recording and numerical approaches, Cardiovascular Research, 10.1093/cvr/cvx117, 113, 10, 1243-1255, 2017.08, Aims Transient receptor potential cation channel subfamily melastatin member 4 (TRPM4), a Ca 2+ -activated nonselective cation channel abundantly expressed in the heart, has been implicated in conduction block and other arrhythmic propensities associated with cardiac remodelling and injury. The present study aimed to quantitatively evaluate the arrhythmogenic potential of TRPM4. Methods and results Patch clamp and biochemical analyses were performed using expression system and an immortalized atrial cardiomyocyte cell line (HL-1), and numerical model simulation was employed. After rapid desensitization, robust reactivation of TRPM4 channels required high micromolar concentrations of Ca 2+. However, upon evaluation with a newly devised, ionomycin-permeabilized cell-attached (Iono-C/A) recording technique, submicromolar concentrations of Ca 2+ (apparent K d = ∼500 nM) were enough to activate this channel. Similar submicromolar Ca 2+ dependency was also observed with sharp electrode whole-cell recording and in experiments coexpressing TRPM4 and L-type voltage-dependent Ca 2+ channels. Numerical simulations using a number of action potential (AP) models (HL-1, Nygren, Luo-Rudy) incorporating the Ca 2+ - and voltage-dependent gating parameters of TRPM4, as assessed by Iono-C/A recording, indicated that a few-fold increase in TRPM4 activity is sufficient to delay late AP repolarization and further increases (≥ six-fold) evoke early afterdepolarization. These model predictions are consistent with electrophysiological data from angiotensin II-treated HL-1 cells in which TRPM4 expression and activity were enhanced. Conclusions These results collectively indicate that the TRPM4 channel is activated by a physiological range of Ca 2+ concentrations and its excessive activity can cause arrhythmic changes. Moreover, these results demonstrate potential utility of the first AP models incorporating TRPM4 gating for in silico assessment of arrhythmogenicity in remodelling cardiac tissue..
15. 仲矢 道雄, 渡健治, 田島充, TAKEO NAKAYA, 松田翔一, 西原弘朗, 山口裕嗣, 橋本明子, 西田光甫, AKIOMI NAGASAKA, 堀井雄馬, 小野達貴, Gentaro Iribe, Ryuji Inoue, TSUDA MAKOTO, Kazuhide Inoue, Akira Tanaka, Masahiko Kuroda, Shigekazu Nagata, Cardiac myofibroblast engulfment of dead cells facilitates recovery after myocardial infarction, JOURNAL OF CLINICAL INVESTIGATION, 10.1172/JCI83822, 127, 1, 383-401, 2017.01, 心筋梗塞時に心臓の線維化を担うのみと考えられていた筋線維芽細胞が、心筋梗塞時の死細胞を貪食する機能を持つことを世界に先駆けて見出した。そして、その貪食がMFG-E8という分子を介して行われていることを見出した。さらに、そのMFG-E8タンパク質を心筋梗塞後の心臓に投与すると、心筋梗塞後の死細胞の貪食が亢進し、心筋梗塞後の病態が改善することを見出した。.
16. Tomoki Takeda, Yukiko Komiya, Takayuki Koga, Takumi Ishida, Yuji Ishii, Yasushi Kikuta, Nakaya Michio, Hitoshi Kurose, Takehiko Yokomizo, Takao Shimizu, Uchi Hiroshi, Masutaka Furue, Hideyuki Yamada, Dioxin-induced increase in leukotriene B4 biosynthesis through the aryl hydrocarbon receptor and its relevance to hepatotoxicity owing to neutrophil infiltration, Journal of Biological Chemistry, 10.1074/jbc.M116.764332, 292, 25, 10586-10599, 2017.01, Dioxin and related chemicals alter the expression of a number of genes by activating the aryl hydrocarbon receptors (AHR) to produce a variety of disorders including hepatotoxicity. However, it remains largely unknown how these changes in gene expression are linked to toxicity. To address this issue, we initially examined the effect of 2,3,7,8-tetrachrolodibenzo-p-di-oxin (TCDD), a most toxic dioxin, on the hepatic and serum metabolome in male pubertal rats and found that TCDD causes many changes in the level of fatty acids, bile acids, amino acids, and their metabolites. Among these findings was the discovery that TCDD increases the content of leukotriene B4 (LTB4), an inducer of inflammation due to the activation of leukocytes, in the liver of rats and mice. Further analyses suggested that an increase in LTB4 comes from a dual mechanism consisting of an induction of arachidonate lipoxygenase-5, a rate-limiting enzyme in LTB4 synthesis, and the down-regulation of LTC4 synthase, an enzyme that converts LTA4 to LTC4. The above changes required AHR activation, because the same was not observed in AHR knock-out rats. In agreement with LTB4 accumulation, TCDD caused the marked infiltration of neutrophils into the liver. However, deleting LTB4 receptors (BLT1) blocked this effect. A TCDD-produced increase in the mRNA expression of inflammatory markers, including tumor-necrosis factor and hepatic damage, was also suppressed in BLT1-null mice. The above observations focusing on metabolomic changes provide novel evidence that TCDD accumulates LTB4 in the liver by an AHR-dependent induction of LTB4 biosynthesis to cause hepatotoxicity through neutrophil activation..
17. Yuki Ohba, Michio Nakaya, The physiological role of G protein-coupled receptor kinase, Seikagaku. The Journal of Japanese Biochemical Society, 87, 5, 612-616, 2015.10.
18. Ayaka Tobo, Masayuki Tobo, Takashi Nakakura, Masashi Ebara, Hideaki Tomura, Chihiro Mogi, Dong-Soon Im, Naoya Murata, Atsushi Kuwabara, Saki Ito, Hayato Fukuda, Mitsuhiro Arisawa, Satoshi Shuto, 仲矢 道雄, 黒瀬 等, Koichi Sato, Fumikazu Okajima, Characterization of Imidazopyridine Compounds as Negative Allosteric Modulators of Proton-Sensing GPR4 in Extracellular Acidification-Induced Responses, PLoS ONE, doi: 10.1371/journal.pone.0129334, 10, 6, e0129334, 2015.06.
19. Ayaka Tobo, Masayuki Tobo, Takashi Nakakura, Masashi Ebara, Hideaki Tomura, Chihiro Mogi, Dong Soon Im, Naoya Murata, Atsushi Kuwabara, Saki Ito, Hayato Fukuda, Mitsuhiro Arisawa, Satoshi Shuto, Michio Nakaya, Hitoshi Kurose, Koichi Sato, Fumikazu Okajima, Characterization of imidazopyridine compounds as negative allosteric modulators of proton-sensing GPR4 in extracellular acidification-induced responses, PloS one, 10.1371/journal.pone.0129334, 10, 6, 2015.06, G protein-coupled receptor 4 (GPR4), previously proposed as the receptor for sphingosylphosphorylcholine, has recently been identified as the proton-sensing G protein-coupled receptor (GPCR) coupling to multiple intracellular signaling pathways, including the Gs protein/cAMP and G13 protein/Rho. In the present study, we characterized some imidazopyridine compounds as GPR4 modulators that modify GPR4 receptor function. In the cells that express proton-sensing GPCRs, including GPR4, OGR1, TDAG8, and G2A, extracellular acidification stimulates serum responsive element (SRE)-driven transcriptional activity, which has been shown to reflect Rho activity, with different proton sensitivities. Imidazopyridine compounds inhibited the moderately acidic pH-induced SRE activity only in GPR4-expressing cells. Acidic pH-stimulated cAMP accumulation, mRNA expression of inflammatory genes, and GPR4 internalization within GPR4-expressing cells were all inhibited by the GPR4 modulator. We further compared the inhibition property of the imidazopyridine compound with psychosine, which has been shown to selectively inhibit actions induced by proton-sensing GPCRs, including GPR4. In the GPR4 mutant, in which certain histidine residues were mutated to phenylalanine, proton sensitivity was significantly shifted to the right, and psychosine failed to further inhibit acidic pH-induced SRE activation. On the other hand, the imidazopyridine compound almost completely inhibited acidic pH-induced action in mutant GPR4. We conclude that some imidazopyridine compounds show specificity to GPR4 as negative allosteric modulators with a different action mode from psychosine, an antagonist susceptible to histidine residues, and are useful for characterizing GPR4-mediated acidic pH-induced biological actions..
20. 大場悠生, 仲矢 道雄, 渡健治, AKIOMI NAGASAKA, 黒瀬 等, GRK6 phosphorylates IκBα at Ser32/Ser36 and enhances TNF-α-induced inflammation, Biochem. Biophys. Res. Commun, doi:10.1016/j.bbrc.2015.04.027, 461, 307-313, 2015.04.
21. Islam A.A.E-H. Ibrahim, Nakaya Michio, Hitoshi Kurose, Ezrin, Radixin, and Moesin Phosphorylation in NIH3T3 Cells Revealed Angiotensin II Type 1 Receptor Cell-Type-Dependent Biased Signaling., J. Pharmacol. Sci, 122, 1-9, 2013.05.
22. Nakaya Michio, 渡健治, Motohiro Nishida, Kyeong-Man Kim, Hitoshi Kurose, β-arrestin2 in infiltrated macrophages inhibits excessive inflammation after myocardial infarction, PLoS One, 8(7), e68351, 2013.05.
23. Nakaya Michio, Mitsuru Tajima, Hidetaka Kosako, Takeo Nakaya, Hiroaki Nishihara, Mina Ohba, Shiori Komiya, Naoki Tani, Motohiro Nishida, Hisaaki Taniguchi, Yoji Sato, Mitsuru Matsumoto, TSUDA MAKOTO, Masahiko Kuroda, Kazuhide Inoue, Hitoshi Kurose, GRK6 deficiency in mice causes autoimmune disease due to impaired apoptotic cell clearance., Nat. Commun. , 287, 1532, 2013.02, 生体内で死んだ細胞はマクロファージなどの貪食細胞によって積極的に取り込まれ、消化されて無くなってしまいます。この速やかな貪食は、死んだ細胞からの内容物の流出を防ぐ等、生体の恒常性を維持する上で極めて重要な役割を担っています。九州大学大学院薬学研究院薬効安全性学分野の黒瀬等教授と仲矢道雄准教授を中心とする研究グループ(九州大学大学院薬学研究院薬理学分野の井上和秀主幹教授、東京医科大学分子病理学講座の黒田雅彦主任教授、徳島大学疾患酵素学センター疾患プロテオミクス研究部門の小迫英尊准教授ら)は、このアポトーシス細胞の貪食にGRK6というタンパク質が関与している事を世界で初めて見出しました。GRK6を欠損したマウスは貪食能の低下が原因で全身性エリテマトーデスや鉄過剰症様の症状を呈しました。従って、GRK6はこれら疾患の治療に関する新たなターゲット分子となることが期待されます。
 本研究成果は、平成25年2月26日(火)(現地時間)に英国科学雑誌 「Nature Communications」オンライン版に掲載されました。.
24. Noriko Makita, Yoji Kabasawa, Yuko Otani, Firman, Junichiro Sato, Makiko Hashimoto, Nakaya Michio, Hiroaki Nishihara, Masaomi Nangaku, Hitoshi Kurose, Tomohiko Ohwada, Taroh Iiri, Attenuated desensitization of β-adrenergic receptor by water-soluble N-nitrosamines that induce S-nitrosylation without NO release., Circ. Res. , 112, 327-334, 2013.01.
25. Nakaya Michio, Chikura Satsuki, Watari Kenji, Mizuno Natsumi, Mochinaga Koji, Supachoke Mangmool, Koyanagi Satoru, shigehiro ohdo, Sato Yoji, Ide Tomomi, Motohiro Nishida, Hitoshi Kurose, Induction of cardiac fibrosis by β-blocker in G protein-independent but GRK5/β-arrestin2-dependent signaling pathways. , J. Biol. Chem. , 287, 35669-35677, 2012.08.
26. Nishioka K, Nishida M, Ariyoshi M, Jian Z, Saiki S, Hirano M, Nakaya M, Sato Y, Kita S, Iwamoto T, Hirano K, Inoue R, Kurose H., Cilostazol suppresses angiotensin II-induced vasoconstriction via protein kinase A-mediated phosphorylation of the transient receptor potential canonical 6 channel., Arterioscler Thromb Vasc Biol, 31, 10, 2278-2286, 2011.10.
27. Kitajima N, Watanabe K, Morimoto S, Sato Y, Kiyonaka S, Hoshijima M, Ikeda Y, Nakaya M, Ide T, Mori Y, Kurose H, Nishida M., TRPC3-mediated Ca(2+) influx contributes to Rac1-mediated production of reactive oxygen species in MLP-deficient mouse hearts, Biochemical and Biophysical Research Communications, 409, 1, 108-113, 2011.05.
28. Nishida M, Ogushi M, Suda R, Toyotaka M, Saiki S, Kitajima N, Nakaya M, Kim KM, Ide T, Sato Y, Inoue K, Kurose H, Heterologous down-regulation of angiotensin type 1 receptors by purinergic P2Y2 receptor stimulation through S-nitrosylation of NF-{kappa}B., Proc Natl Acad Sci U S A, 108, 16, 6662-6667, 2011.04.
29. Motohiro Nishida, Reiko Suda, Yuichi Nagamatsu, Shihori Tanabe, Naoya Onohara, Michio Nakaya, Yasunori Kanaho, Takahiro Shibata, Koji Uchida, Hideki Sumimoto, Yoji Sato, & Hitoshi Kurose. , Pertussis toxin upregulates angiotensin type1 receptors through TLR4-mediated Rac activation., Journal of Biological Chemistry, 285, 20, 15268-15277, 2010.05.
30. Motohiro Nishida, Kenta Watanabe, Yoji Sato, Michio Nakaya, Naoyuki Kitajima, Tomomi Ide, Ryuji Inoue, & Hitoshi Kurose., Phosphorylation of TRPC6 channels at Thr69 is required for anti-hypertrophic effects of phosphodiesterase 5 inhibition., Journal of Biological Chemistry, 2010.04.
31. Nishida M, Sato Y, Uemura A, Narita Y, Toazaki-Saitoh H, Nakaya M, Ide T, Suzuki K, Inoue K, Nagao T, Kurose H., P2Y6 receptor-Galpha12/13 signalling in cardiomyocytes triggers pressure overload-induced cardiac fibrosis., EMBO Journal, 27(23) 3104-3115., 2008.12.
32. Michio Nakaya, Masahiro Kitano, Michiyuki Matsuda, Shigekazu Nagata, Spatiotemporal regulation of Rac1 to control actin patch for engulfment of apoptotic cells, Proceedings of the National Academy of Sciences, 105 (27) 9198-9203, 2008.07.
33. Masahiro Kitano, Michio Nakaya, Takeshi Nakamura, Shigekazu Nagata, Michiyuki Matsuda, Imaging of Rab5 activity identifies essential regulators for phagosome maturation, Nature, 453 (7192) 241-245, 2008.05.
34. Nakaya M, Tanaka M, Okabe Y, Hanayama R, Nagata S, Opposite effects of Rho family GTPases on engulfment of apoptotic cells by macrophages., Journal of Biological Chemistry, 281(13) 8836-8842, 2006.03.
35. Nakaya M, Sanada K, & Fukada Y., Spatial and temporal regulation of mitogen-activated protein kinase phosphorylation in the mouse suprachiasmatic nucleus, Biochem. Biophys. Res. Commun., 305 (3) 494-501, 2003.06.