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Affiliation |
Faculty of Medicine School of Medicine Department of Medical Sciences, Pharmacology |
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Assistant Professor |
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External Link |
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MIURA Ayako
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Research Areas 【 display / non-display 】
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Life Science / Respiratory medicine
Papers 【 display / non-display 】
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The NERP-4–SNAT2 axis regulates pancreatic β-cell maintenance and function Reviewed International coauthorship
Weidong Zhang, Ayako Miura, Md Moin Abu Saleh, Koichiro Shimizu, Yuichiro Mita, Ryota Tanida, Satoshi Hirako, Seiji Shioda, ValeryGmyr, Julie Kerr-Conte, Francois Pattou,Chunhuan Jin, Yoshikatsu Kanai, Kazuki Sasaki, Naoto Minamino, Hideyuki Sakoda & Masamitsu Nakazato
Nature Communications 14 ( 8158 ) 2023.12
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
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The NERP-4–SNAT2 axis regulates pancreatic β-cell maintenance and function Reviewed
Zhang W., Miura A., Abu Saleh M.M., Shimizu K., Mita Y., Tanida R., Hirako S., Shioda S., Gmyr V., Kerr-Conte J., Pattou F., Jin C., Kanai Y., Sasaki K., Minamino N., Sakoda H., Nakazato M.
Nature Communications 14 ( 1 ) 2023.12
Publishing type：Research paper (scientific journal) Publisher：Nature Communications
Insulin secretion from pancreatic β cells is regulated by multiple stimuli, including nutrients, hormones, neuronal inputs, and local signalling. Amino acids modulate insulin secretion via amino acid transporters expressed on β cells. The granin protein VGF has dual roles in β cells: regulating secretory granule formation and functioning as a multiple peptide precursor. A VGF-derived peptide, neuroendocrine regulatory peptide-4 (NERP-4), increases Ca2+ influx in the pancreata of transgenic mice expressing apoaequorin, a Ca2+-induced bioluminescent protein complex. NERP-4 enhances glucose-stimulated insulin secretion from isolated human and mouse islets and β-cell–derived MIN6-K8 cells. NERP-4 administration reverses the impairment of β-cell maintenance and function in db/db mice by enhancing mitochondrial function and reducing metabolic stress. NERP-4 acts on sodium-coupled neutral amino acid transporter 2 (SNAT2), thereby increasing glutamine, alanine, and proline uptake into β cells and stimulating insulin secretion. SNAT2 deletion and inhibition abolish the protective effects of NERP-4 on β-cell maintenance. These findings demonstrate a novel autocrine mechanism of β-cell maintenance and function that is mediated by the peptide–amino acid transporter axis.
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Matsuo A, Tanida R, Yanagi S, Tsubouchi H, Miura A, Shigekusa T, Matsumoto N, Nakazato M
European journal of pharmacology 892 173754 2021.2
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：European Journal of Pharmacology
© 2020 The Authors Fibrotic scarring is an important prognostic factor of acute respiratory distress syndrome (ARDS). There are currently no antifibrotic drugs or other therapeutic agents for ARDS. Lysyl oxidase-like 2 (LOXL2), an amine oxidase, contributes to fibrotic scarring by facilitating collagen cross-linking. Recent clinical trials revealed that a monoclonal inhibitory antibody against LOXL2 failed to show benefit over placebo in patients with fibrotic disorders involving the lungs. These clinical results raise the possibility that targeting the extracellular enzymic activity of LOXL2 is not in itself sufficient to prevent fibrotic scarring. We investigated the role of LOXL2 in the pathogenesis of ARDS in vivo, in vitro, and in samples from patients with ARDS. After lung injury, LOXL2 was unevenly expressed in the nuclei of lung fibroblasts and myofibroblasts in the fibrotic phase. Nuclear LOXL2 expression was upregulated in lung fibroblasts after transforming growth factor-beta1 (TGF-β1)-treatment. LOXL2 silencing abrogated the TGF-β1-induced expression of a myofibrogenic-progenitor marker, the appearance of proto-myofibroblasts, and the evolution of differentiated myofibroblasts in lung fibroblasts. Nuclear upregulation of Snail was evident in myofibroblasts during the fibrotic phase after lung injury. We detected high levels of LOXL2 protein in the lungs of ARDS patients, specifically during the proliferative and fibrotic phases. Our results highlight nuclear LOXL2 in fibroblasts as a primary causative driver of cell-fate decision toward myofibroblasts and of the progression of fibrotic scarring. A nuclear-LOXL2-targeted agent could be a promising therapeutic strategy against fibrotic disorders including ARDS.
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Ishii N, Tsubouchi H, Miura A, Yanagi S, Ueno H, Shiomi K, Nakazato M
European Journal of Pharmacology 819 35 - 42 2018.1
Language：English Publishing type：Research paper (scientific journal) Publisher：European Journal of Pharmacology
© 2017 Elsevier B.V. Paclitaxel is an effective chemotherapeutic agent, but has some treatment-limiting adverse effects that markedly decrease patients’ quality of life. Peripheral neuropathy is one of these, and no treatment for it has been established yet. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is secreted from the stomach and has widespread effects on multiple systems. We investigated the pharmacological potential of ghrelin in preventing paclitaxel-induced peripheral neuropathy using wild-type mice, ghrelin-null mice, and growth hormone secretagogue receptor-null mice. In wild-type mice, ghrelin administration alleviated mechanical and thermal hypersensitivity, and partially prevented neuronal loss of small unmyelinated intraepidermal nerve fibers but not large myelinated nerve fibers. Moreover, ghrelin administration decreased plasma oxidative and nitrosative stress and increased the expression of uncoupling protein 2 (UCP2) and superoxide dismutase 2 (SOD2) in the dorsal root ganglia, which are mitochondrial antioxidant proteins, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a regulator of mitochondrial number. Both ghrelin-null mice and growth hormone secretagogue receptor-null mice developed more severe nerve injuries than wild-type mice. Our results suggest that ghrelin administration exerts a protective effect against paclitaxel-induced neuropathy by reducing oxidative stress and enhancing mitochondrial anti-oxidant functions, and that endogenous ghrelin has a neuroprotective effect that is mediated by ghrelin/growth hormone secretagogue receptor signaling. Ghrelin could be a promising therapeutic agent for the management of this intractable disease.
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Neuromedin U suppresses glucose-stimulated insulin secretion in pancreatic β cells Reviewed
Zhang W,Sakoda H,Miura A,Shimizu K,Mori K,Miyazato M,Takayama K,Hayashi Y,Nakazato M
Biochemical and Biophysical Research Communications 493 ( 1 ) 677 - 683 2017.11
Language：English Publishing type：Research paper (scientific journal) Publisher：Biochemical and Biophysical Research Communications
© 2017 The Authors Neuromedin U (NMU), a highly conserved peptide in mammals, is implicated in energy homeostasis and glycemic control, and may also be involved in the regulation of adipoinsular axis function. However, the role of NMU in regulating insulin secretion has not been clearly established. In this study, we investigated the role of NMU in the regulation of insulin secretion both in vitro and in vivo. We found that NMU and NMU receptor (NMUR) 1 were expressed in mouse islets and β cell-derived MIN6-K8 cells. In mice, NMU suppressed glucose-stimulated insulin secretion (GSIS) both in vitro and in vivo. Additionally, an NMUR1 agonist inhibited GSIS in both MIN6-K8 cells and mice islets. Moreover, NMU attenuated intracellular Ca2+ influx in MIN6-K8 cells, potentially causing a decrease in insulin secretion. siNmu-transfected MIN6-K8 cells showed elevated GSIS. Treatment with anti-NMU IgG increased GSIS in isolated mouse pancreatic islets. These results suggested that NMU can act directly on β cells through NMUR1 in an autocrine or paracrine fashion to suppress insulin secretion. Collectively, our results highlight the crucial role of NMU in suppressing pancreatic insulin secretion, and may improve our understanding of glucose homeostasis.
Presentations 【 display / non-display 】
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Role of ERM proteins in the regulation of actin cytoskeleton in migrating alveolar macrophage
Ayako Miura，Fumiyuki Sanematsu，Ryu Takeya
2023.12
Event date： 2023.12.14 - 2023.12.16
Language：English Presentation type：Poster presentation
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Regulation of directional cell motility in alveolar macrophages by a formin family protein Fhod1
Ayako Miura，Fumiyuki Sanematsu，Ryu Takeya
2022.11
Event date： 2022.11.30 - 2022.12.3
Language：English Presentation type：Poster presentation
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ARDS線維化過程におけるfibroblast/myofibroblastの核内LOXL2阻害の意義
松尾彩子、谷田亮太、柳 重久、坪内拡伸、三浦綾子、重草貴文、松元信弘、中里雅光、宮崎泰可
第62回日本呼吸器学会学術講演会 2022.4
Event date： 2022.4.22 - 2022.4.24
Language：Japanese Presentation type：Oral presentation (general)
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The actin-nucleating protein Fhod1 in alveolar macrophage
Ayako Miura，Fumiyuki Sanamatsu，Ryu Takeya
2022.3
Event date： 2022.3.7 - 2022.3.9
Language：English Presentation type：Poster presentation
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NMU induces β cell failure by triggering mitochondrial dysfunction and ER stress
張維東、迫田秀之、三浦綾子、中里雅光
AMED-CREST International Symposium. Miyazaki.
Event date： 2020.1.31 - 2020.2.2
Language：English Presentation type：Poster presentation
Awards 【 display / non-display 】
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ERS Young Scientist Sponsorship
2016.9 Europian Respiratory Society The role of Pten in the cell-fate determination of epithelial cells in lung development.
三浦綾子
Award type：Award from international society, conference, symposium, etc. Country：United Kingdom
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Kyushu Diabetes Research Conference 最優秀奨励賞
2016.7 Kyusyu Diabetes Research Conference 糖代謝調節に機能する新規生理活性ペプチドの発見
三浦綾子
Award type：Award from Japanese society, conference, symposium, etc. Country：Japan
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児玉記念基礎医学助成基金 優秀研究論文顕彰
2013.10 児玉記念基礎医学助成基金 Pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1) gene is suppressed by transglutaminase 2 activation.
三浦綾子
Award type：Award from publisher, newspaper, foundation, etc. Country：Japan
Grant-in-Aid for Scientific Research 【 display / non-display 】
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異種細胞間の細胞接着装置の恒常性維持機構の解析
Grant number：21K08183 2021.04 - 2024.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究（C)
Authorship：Principal investigator
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サルコメアは回転トルクを生み出すか？
Grant number：22K19407 2022.04 - 2024.03
独立行政法人日本学術振興会 科学研究費補助金 挑戦的研究（萌芽）
武谷 立、
Authorship：Coinvestigator(s)
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The Role of Epithelial Pten in Epithelial Cell Fate and Programmed Cellular Senescence during Lung Development
Grant number：17K16051 2017.04 - 2021.03
Grant-in-Aid for Scientific Research Grant-in-Aid for Young Scientists(B)
Authorship：Principal investigator
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上皮間葉連関を焦点とした肺発生での上皮Ptenの機能解析
Grant number：26860610 2014.04 - 2016.03
科学研究費補助金 若手研究(B)
Authorship：Principal investigator