Organization
Nagoya University Hospital Nephrology Lecturer
Graduate School
Graduate School of Medicine
Title
Lecturer
KATO Noritoshi
Degree 1
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博士（医学） （ 2009.7 名古屋大学 ）
Research Interests 4
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microRNA
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遺伝学的検査
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遺伝子治療
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Polycystic kidney
Research Areas 2
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Life Science / Nephrology
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Life Science / Genetics
Professional Memberships 2
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日本透析医学会
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日本腎臓学会
Papers 61
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Tsuboi, T; Hattori, K; Ishimoto, T; Imai, K; Doke, T; Hagita, J; Ariyoshi, J; Furuhashi, K; Kato, N; Ito, Y; Kamiya, Y; Asanuma, H; Maruyama, S
MOLECULAR THERAPY NUCLEIC ACIDS Vol. 36 ( 1 ) page： 102387 2025.3
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Maruyama, S; Ikeda, Y; Kaname, S; Kato, N; Matsumoto, M; Ishikawa, Y; Shimono, A; Miyakawa, Y; Nangaku, M; Shibagaki, Y; Okada, H
JOURNAL OF NEPHROLOGY Vol. 37 ( 8 ) page： 2181 - 2190 2024.11
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Sugiura, T; Doke, T; Tanaka, A; Sato, Y; Maeda, K; Furuhashi, K; Kato, N; Kosugi, T; Maruyama, S
CEN CASE REPORTS 2024.9
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Tatematsu, Y; Imaizumi, T; Michihata, N; Kato, N; Kumazawa, R; Matsui, H; Fushimi, K; Yasunaga, H; Maruyama, S
SCIENTIFIC REPORTS Vol. 14 ( 1 ) page： 18265 2024.8
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Detecting and exploring kidney-derived extracellular vesicles in plasma
Komatsu, S; Kato, N; Kitai, H; Funahashi, Y; Noda, Y; Tsubota, S; Tanaka, A; Sato, Y; Maeda, K; Saito, S; Furuhashi, K; Ishimoto, T; Kosugi, T; Maruyama, S; Kadomatsu, K
CLINICAL AND EXPERIMENTAL NEPHROLOGY Vol. 28 ( 7 ) page： 617 - 628 2024.7
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Nishibori, N; Okazaki, M; Miura, Y; Hishida, M; Kurasawa, S; Imaizumi, T; Kato, N; Kosugi, T; Kuro-o, M; Kasuga, H; Kaneda, F; Maruyama, S
CLINICAL KIDNEY JOURNAL Vol. 17 ( 6 ) page： sfae121 2024.6
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Yasuda, Y; Kaihan, AB; Kaihan, AN; Tanaka, A; Imaizumi, T; Maeda, K; Kato, N; Kosugi, T; Maruyama, S
NEPHROLOGY DIALYSIS TRANSPLANTATION Vol. 39 2024.5
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Yasuda, Y; Kaihan, AB; Kaihan, AN; Tanaka, A; Imaizumi, T; Maeda, K; Kato, N; Kosugi, T; Maruyama, S
NEPHROLOGY DIALYSIS TRANSPLANTATION Vol. 39 page： I736 - I737 2024.5
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Rationale and design of the Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study
Kurasawa, S; Kato, S; Ozeki, T; Akiyama, S; Ishimoto, T; Mizuno, M; Tsuboi, N; Kato, N; Kosugi, T; Maruyama, S
CLINICAL AND EXPERIMENTAL NEPHROLOGY Vol. 28 ( 5 ) page： 431 - 439 2024.5
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Tasaki, Y; Tsujimoto, H; Yokoyama, T; Sugimoto, N; Kitajima, S; Fujii, H; Hidaka, Y; Kato, N; Maruyama, S; Inoue, N; Wada, T
FRONTIERS IN IMMUNOLOGY Vol. 15 page： 1360855 2024.3
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Nakamura, Y; Kato, N; Tatematsu, Y; Arai, Y; Mori, N; Shibata, K; Yamazaki, M; Yasui, H; Fujiwara, S; Yamakawa, T; Maruyama, S
CEN CASE REPORTS Vol. 13 ( 1 ) page： 37 - 44 2024.2
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Osawa, K; Yamamoto, S; Yamano, Y; Kita, A; Okamoto, K; Kato, N; Tatematsu, Y; Kojima, F; Ohya, M; Hara, S; Murata, SI; Inoue, N; Maruyama, S; Araki, SI
INTERNAL MEDICINE Vol. 63 ( 12 ) page： 1777 - 1782 2024
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Watanabe, T; Maeda, K; Kato, N; Seko, H; Sugimura, M; Sato, Y; Ryuge, A; Kato, S; Kadomatsu, K; Maruyama, S; Kosugi, T
NEPHROLOGY Vol. 28 ( 11 ) page： 629 - 638 2023.11
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Muto, R; Maeda, K; Fukui, S; Saito, S; Kato, N; Kosugi, T; Shimizu, A; Maruyama, S
CEN CASE REPORTS Vol. 12 ( 3 ) page： 323 - 328 2023.8
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Uwatoko, R; Shindo, M; Hashimoto, N; Iio, R; Ueda, Y; Tatematsu, Y; Kato, N; Maruyama, S; Hayashi, T
JOURNAL OF NEPHROLOGY Vol. 36 ( 5 ) page： 1439 - 1442 2023.6
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Wada, H; Teranishi, H; Shimono, A; Kato, N; Maruyama, S; Matsumoto, M
THROMBOSIS JOURNAL Vol. 21 ( 1 ) page： 43 2023.4
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Sato, N; Inagaki, K; Takanashi, M; Muto, R; Kato, N; Maruyama, S; Akahori, T
INTERNAL MEDICINE Vol. 62 ( 19 ) page： 2865 - 2870 2023
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Systematic characterization of seed overlap microRNA cotargeting associated with lupus pathogenesis
Kitai, H; Kato, N; Ogami, K; Komatsu, S; Watanabe, Y; Yoshino, S; Koshi, E; Tsubota, S; Funahashi, Y; Maeda, T; Furuhashi, K; Ishimoto, T; Kosugi, T; Maruyama, S; Kadomatsu, K; Suzuki, H
BMC BIOLOGY Vol. 20 ( 1 ) page： 248 2022.11
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Otsuka, T; Izumi, T; Nishihori, M; Tsukada, T; Goto, S; Ikezawa, M; Kato, N; Nakano, M; Uda, K; Yokoyama, K; Araki, Y; Saito, R
NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 84 ( 4 ) page： 884 - 889 2022.11
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Kita, T; Ashizuka, S; Takeda, T; Matsumoto, T; Ohmiya, N; Nakase, H; Motoya, S; Ohi, H; Mitsuyama, K; Hisamatsu, T; Kanmura, S; Kato, N; Ishihara, S; Nakamura, M; Moriyama, T; Saruta, M; Nozaki, R; Yamamoto, S; Inatsu, H; Watanabe, K; Kitamura, K
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Vol. 37 ( 11 ) page： 2051 - 2059 2022.11
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Maruyama, S; Ikeda, Y; Kaname, S; Kato, N; Matsumoto, M; Ishikawa, Y; Shimono, A; Miyakawa, Y; Nangaku, M; Shibagaki, Y; Okada, H
NEPHROLOGY DIALYSIS TRANSPLANTATION Vol. 37 page： I231 - I232 2022.5
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Minatoguchi, S; Saito, S; Furuhashi, K; Sawa, Y; Okazaki, M; Shimamura, Y; Kaihan, AB; Hashimoto, Y; Yasuda, Y; Hara, A; Mizutani, Y; Ando, R; Kato, N; Ishimoto, T; Tsuboi, N; Esaki, N; Matsuyama, M; Shiraki, Y; Kobayashi, H; Asai, N; Enomoto, A; Maruyama, S
SCIENTIFIC REPORTS Vol. 12 ( 1 ) page： 5389 2022.3
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The 30-year Natural History of Non-classic Fabry Disease with an R112H Mutation
Muto, R; Inagaki, K; Kato, N; Maruyama, S; Akahori, T
INTERNAL MEDICINE Vol. 61 ( 11 ) page： 1727 - 1730 2022
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Rossanti, R; Nozu, K; Fukunaga, A; Nagano, C; Horinouchi, T; Yamamura, T; Sakakibara, N; Minamikawa, S; Ishiko, S; Aoto, Y; Okada, E; Ninchoji, T; Kato, N; Maruyama, S; Kono, K; Nishi, S; Iijima, K; Fujii, H
CLINICAL AND EXPERIMENTAL NEPHROLOGY Vol. 25 ( 11 ) page： 1224 - 1230 2021.11
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Basigin deficiency prevents anaplerosis and ameliorates insulin resistance and hepatosteatosis
Ryuge, A; Kosugi, T; Maeda, K; Banno, R; Gou, Y; Zaitsu, K; Ito, T; Sato, Y; Hirayama, A; Tsubota, S; Honda, T; Nakajima, K; Ozaki, T; Kondoh, K; Takahashi, K; Kato, N; Ishimoto, T; Soga, T; Nakagawa, T; Koike, T; Arima, H; Yuzawa, Y; Minokoshi, Y; Maruyama, S; Kadomatsu, K
JCI INSIGHT Vol. 6 ( 20 ) 2021.10
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Kato, N; Hasegawa, T; Muto, R; Tanaka, A; Sato, Y; Maeda, K; Furuhashi, K; Saito, S; Kosugi, T; Maruyama, S
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Vol. 32 ( 10 ) page： 823 - 824 2021.10
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Miyabe, Y; Nakai, A; Watanabe, K; Karasawa, K; Kato, N; Maruyama, S; Moriyama, T; Nitta, K
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Vol. 32 ( 10 ) page： 826 - 827 2021.10
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Hachiya, A; Karasawa, M; Imaizumi, T; Kato, N; Katsuno, T; Ishimoto, T; Kosugi, T; Tsuboi, N; Maruyama, S
SCIENTIFIC REPORTS Vol. 11 ( 1 ) page： 1525 2021.1
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Acquired Fanconi Syndrome in a Patient with Nontyphoidal <i>Salmonella</i> Bacteremia
Ryuge, A; Saito, S; Morioka, H; Hachiya, A; Kato, N; Ishimoto, T; Kosugi, T; Maruyama, S
INTERNAL MEDICINE Vol. 60 ( 5 ) page： 761 - 764 2021
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Refractory Hypotension Caused by Selenium Deficiency in a Patient on Peritoneal Dialysis
Ryuge, A; Kim, H; Suzuki, Y; Okazaki, M; Kojima, H; Saito, S; Kato, N; Ishimoto, T; Kosugi, T; Maruyama, S; Mizuno, M
INTERNAL MEDICINE Vol. 60 ( 15 ) page： 2461 - 2464 2021
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THE ROLE OF FRUCTOSE METABOLISM IN VASCULAR ENDOTHELIAL FUNCTION IN DIABETES
Ishimoto, T; Doke, T; Hayasaki, T; Kato, N; Maruyama, S
NEPHROLOGY Vol. 25 page： 62 - 62 2020.10
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EXOSOMES FROM CKD PATIENTS HAVE ATHEROSCLEROGENIC PROPERTIES
Kato, N; Nishio, F; Ishimoto, T; Kosugi, T; Maruyama, S
NEPHROLOGY Vol. 25 page： 62 - 62 2020.10
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Endothelial-to-mesenchymal transition compromises vascular integrity to induce Myc-mediated metabolic reprogramming in kidney fibrosis.
Lovisa S, Fletcher-Sananikone E, Sugimoto H, Hensel J, Lahiri S, Hertig A, Taduri G, Lawson E, Dewar R, Revuelta I, Kato N, Wu CJ, Bassett RL Jr, Putluri N, Zeisberg M, Zeisberg EM, LeBleu VS, Kalluri R
Science signaling Vol. 13 ( 635 ) 2020.6
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Muto, R; Inagaki, K; Sato, N; Sameshima, T; Nagakura, Y; Baba, S; Kato, N; Maruyama, S; Akahori, T
INTERNAL MEDICINE Vol. 59 ( 24 ) page： 3187 - 3193 2020
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Hayasaki, T; Ishimoto, T; Doke, T; Hirayama, A; Soga, T; Furuhashi, K; Kato, N; Kosugi, T; Tsuboi, N; Lanaspa, MA; Johnson, RJ; Maruyama, S; Kadomatsu, K
JOURNAL OF NUTRITIONAL BIOCHEMISTRY Vol. 71 page： 54 - 62 2019.9
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miR-146a targeted to splenic macrophages prevents sepsis-induced multiple organ injury
Funahashi, Y; Kato, N; Masuda, T; Nishio, F; Kitai, H; Ishimoto, T; Kosugi, T; Tsuboi, N; Matsuda, N; Maruyama, S; Kadomatsu, K
LABORATORY INVESTIGATION Vol. 99 ( 8 ) page： 1130 - 1142 2019.8
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CD147/Basigin Deficiency Prevents the Development of Podocyte Injury through FAK Signaling
Yoshioka, T; Kosugi, T; Masuda, T; Watanabe, T; Ryuge, A; Nagaya, H; Maeda, K; Sato, Y; Katsuno, T; Kato, N; Ishimoto, T; Yuzawa, Y; Maruyama, S; Kadomatsu, K
AMERICAN JOURNAL OF PATHOLOGY Vol. 189 ( 7 ) page： 1338 - 1350 2019.7
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Funahashi, Y; Kato, N; Ishimoto, T; Kosugi, T; Maruyama, S
NEPHROLOGY DIALYSIS TRANSPLANTATION Vol. 34 2019.6
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Katsuno T, Masuda T, Saito S, Kato N, Ishimoto T, Kato S, Kosugi T, Tsuboi N, Kitamura H, Tsuzuki T, Ito Y, Maruyama S
Clinical and experimental nephrology Vol. 23 ( 2 ) page： 207 - 214 2019.2
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Essential points from Evidence-based Clinical Practice Guidelines for Chronic Kidney Disease 2018
Okada Hirokazu, Yasuda Yoshinari, Kashihara Naoki, Asahi Koichi, Ito Takafumi, Kaname Shinya, Kanda Eiichiro, Kanno Yoshihiko, Shikata Kenichi, Shibagaki Yugo, Tsuchiya Ken, Tsuruya Kazuhiko, Nagata Daisuke, Narita Ichiei, Nangaku Masaomi, Hattori Motoshi, Hamano Takayuki, Fujimoto Shouichi, Moriyama Toshiki, Yamagata Kunihiro, Yamamoto Ryohei, Wakasugi Minako, Ashida Akira, Usui Joichi, Kawamura Kazuko, Kitamura Kenichiro, Konta Tsuneo, Suzuki Yusuke, Tsuruoka Shuichi, Nishio Saori, Hamano Takayuki, Fujii Naohiko, Fujii Hideki, Wada Takehiko, Yokoyama Hitoshi, Aoki Katsunori, Akiyama Daiichiro, Araki Shin-ichi, Arima Hisatomi, Ishikawa Eiji, Ishikura Kenji, Ishizuka Kiyonobu, Ishimoto Takuji, Ishimoto Yu, Iseki Kunitoshi, Itabashi Mitsuyo, Ichioka Satoko, Ichikawa Kazunobu, Ichikawa Daisuke, Inoue Shuji, Imai Toshimi, Imamura Hideaki, Iwata Yasunori, Iwazu Yoshitaka, Usui Toshiaki, Uchida Keiko, Egawa Masahiro, Ohara Shinichiro, Omori Norio, Okada Rieko, Okuda Yusuke, Ozeki Takaya, Obata Yoko, Kai Hirayasu, Kato Noritoshi, Kanasaki Keizo, Kaneko Yoshikatsu, Kabasawa Hideyuki, Kawaguchi Takehiko, Kawasaki Yukihiko, Kawashima Keisuke, Kawano Haruna, Kikuchi Kan, Kihara Masao, Kimura Yoshiki, Kurita Noriaki, Koike Kentaro, Koizumi Masahiro, Kojima Chiari, Goto Shunsuke, Konomoto Takao, Kohagura Kentaro, Komatsu Hiroyuki, Komaba Hirotaka, Saito Chie, Sakai Yukinao, Sakaguchi Yusuke, Satonaka Hiroshi, Jimi Kanako, Shimizu Akihiro, Shimizu Sayaka, Shirai Sayuri, Shinzawa Maki, Sugiyama Kazuhiro, Suzuki Tomo, Suzuki Hitoshi, Suyama Kazuhide, Segawa Hiroyoshi, Takahashi Kazuya, Tanaka Kenichi, Tanaka Tetsuhiro, Tsunoda Ryoya, Tsuruta Yuki, Nakakura Hyogo, Nagasawa Yasuyuki, Nakanishi Koichi, Nagahama Masahiko, Nakaya Izaya, Nanami Masayoshi, Niihata Kakuya, Nishi Shinichi, Nishiwaki Hiroki, Hasegawa Shoko, Hasegawa Midori, Hanada Ken, Hayashi Hiroki, Harada Ryoko, Hishida Manabu, Hirano Daishi, Hirahashi Junichi, Hirama Akio, Hirayama Kouichi, Fukagawa Masafumi, Fukuda Akihiro, Fujii Yoshiyuki, Fujisaki Kiichiro, Furuya Fumihiko, Hoshino Junichi, Hosojima Michihiro, Honda Kenjiro, Masuda Takahiro, Matsui Kosuke, Matsukuma Yuta, Matsumura Hideki, Mii Akiko, Miura Kenichiro, Mitobe Michihiro, Miyasato Yoshikazu, Miyamoto Satoshi, Miwa Saori, Yazawa Masahiko, Yata Yusuke, Yamamoto Yoshihiro, Watanabe Kimio, Hosojima Michihiro
CLINICAL AND EXPERIMENTAL NEPHROLOGY Vol. 23 ( 1 ) page： 1-15 2019.1
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Katsuno T, Ozaki T, Ozeki T, Hachiya A, Kim H, Kato N, Ishimoto T, Kato S, Kosugi T, Tsuboi N, Mizuno M, Ito Y, Maruyama S
Clinical and experimental nephrology Vol. 22 ( 6 ) page： 1341 - 1350 2018.12
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Lacking ketohexokinase-A exacerbates renal injury in streptozotocin-induced diabetic mice.
Doke T, Ishimoto T, Hayasaki T, Ikeda S, Hasebe M, Hirayama A, Soga T, Kato N, Kosugi T, Tsuboi N, Lanaspa MA, Johnson RJ, Kadomatsu K, Maruyama S
Metabolism: clinical and experimental Vol. 85 page： 161 - 170 2018.8
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The clinical relevance of plasma CD147/basigin in biopsy-proven kidney diseases
Mori Yoshiko, Masuda Tomohiro, Kosugi Tomoki, Yoshioka Tomoki, Hori Mayuko, Nagaya Hiroshi, Maeda Kayaho, Sato Yuka, Kojima Hiroshi, Kato Noritoshi, Ishimoto Takuji, Katsuno Takayuki, Yuzawa Yukio, Kadomatsu Kenji, Maruyama Shoichi
CLINICAL AND EXPERIMENTAL NEPHROLOGY Vol. 22 ( 4 ) page： 815 - 824 2018.8
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Funahashi Yoshio, Kato Noritoshi, Kitai Hiroki, Ishimoto Takuji, Kosugi Tomoki, Tsuboi Naotake, Matsuda Naoyuki, Maruyama Shoichi, Kadomatsu Kenji
SHOCK Vol. 49 ( 6 ) page： 21 - 21 2018.6
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Funahashi Yoshio, Kato Noritoshi, Ozeki Takaya, Kobayashi Azusa, Oishi Hideto, Maruyama Shoichi
SHOCK Vol. 49 ( 6 ) page： 68 - 68 2018.6
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INDUCTION OF IMMUNOSUPPRESSIVE MICRO-RNA IN SPLEEN ATTENUATES SEPSIS INDUCED ACUTE KIDNEY INJURY
Funahashi, Y; Kato, N; Ishimoto, T; Kosugi, T; Tsuboi, N; Kadomatsu, K; Maruyama, S
NEPHROLOGY DIALYSIS TRANSPLANTATION Vol. 32 2017.5
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Masuda Tomohiro, Maeda Kayaho, Sato Waichi, Kosugi Tomoki, Sato Yuka, Kojima Hiroshi, Kato Noritoshi, Ishimoto Takuji, Tsuboi Naotake, Uchimura Kenji, Yuzawa Yukio, Maruyama Shoichi, Kadomatsu Kenji
AMERICAN JOURNAL OF PATHOLOGY Vol. 187 ( 4 ) page： 740 - 751 2017.4
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Sato Naokazu, Katsuno Takayuki, Mori Masayoshi, Saito Shouji, Kato Noritoshi, Ishimoto Takuji, Kosugi Tomoki, Tsuboi Naotake, Ito Yasuhiko, Maruyama Shouichi
RHEUMATOLOGY Vol. 56 page： 75 - 75 2017.3
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Katsuno Takayuki, Ozaki Takenori, Kim Hangsoo, Kato Noritoshi, Suzuki Yasuhiro, Akiyama Shinichi, Ishimoto Takuji, Kosugi Tomoki, Tsuboi Naotake, Ito Yasuhiko, Maruyama Shoichi
INTERNAL MEDICINE Vol. 56 ( 13 ) page： 1679 - 1686 2017
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Increase of Antimyeloperoxidase Antineutrophil Cytoplasmic Antibody (ANCA) in Patients with Renal ANCA-associated Vasculitis: Association with Risk to Relapse. Reviewed
J Rheumatol. page： 1853-60 2015.9
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CD147/basigin limits lupus nephritis and Th17 cell differentiation in mice by inhibiting the interleukin-6/STAT-3 pathway. Reviewed
Maeda K, Kosugi T, Sato W, Kojima H, Sato Y, Kamimura D, Kato N, Tsuboi N, Yuzawa Y, Matsuo S, Murakami M, Maruyama S, Kadomatsu K.
Arthritis Rheumatol. page： 2185-95 2015.5
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The efficacy of tolvaptan as a diuretic for chronic kidney disease patients. Reviewed
Tanaka A, Katsuno T, Ozaki T, Sakata F, Kato N, Suzuki Y, Kosugi T, Kato S, Tsuboi N, Sato W, Yasuda Y, Mizuno M, Ito Y, Matsuo S, Maruyama S.
Acta Cardiol. page： 217-23. 2015.4
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Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Reviewed
Melo SA, Sugimoto H, O'Connell JT, Kato N, Villanueva A, Vidal A, Qiu L, Vitkin E, Perelman LT, Melo CA, Lucci A, Ivan C, Calin GA, Kalluri R
Cancer Cell page： 707-21 2014.11
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CD147/basigin reflects renal dysfunction in patients with acute kidney injury. Reviewed
Nagaya H, Kosugi T, Maeda-Hori M, Maeda K, Sato Y, Kojima H, Hayashi H, Kato N, Ishimoto T, Sato W, Yuzawa Y, Matsuo S, Kadomatsu K, Maruyama S.
Clin Exp Nephrol. page： 746-54 2014.10
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TGF-β1-containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis. Reviewed
Borges FT, Melo SA, Özdemir BC, Kato N, Revuelta I, Miller CA, Gattone VH 2nd, LeBleu VS, Kalluri R.
J Am Soc Nephrol. page： 385-92. 2013.2
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Deficiency of growth factor midkine exacerbates necrotizing glomerular injuries in progressive glomerulonephritis. Reviewed
Kojima H, Kosugi T, Sato W, Sato Y, Maeda K, Kato N, Kato K, Inaba S, Ishimoto T, Tsuboi N, Matsuo S, Maruyama S, Yuzawa Y, Kadomatsu K.
Am J Pathol. page： 410-9 2013.2
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Basigin/CD147 promotes renal fibrosis after unilateral ureteral obstruction. Reviewed
Kato N, Kosugi T, Sato W, Ishimoto T, Kojima H, Sato Y, Sakamoto K, Maruyama S, Yuzawa Y, Matsuo S, Kadomatsu K.
Am J Pathol. page： 572-9. 2011.2
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The E-selectin ligand basigin/CD147 is responsible for neutrophil recruitment in renal ischemia/reperfusion. Reviewed
Kato N, Yuzawa Y, Kosugi T, Hobo A, Sato W, Miwa Y, Sakamoto K, Matsuo S, Kadomatsu K.
J Am Soc Nephrol. page： 1565-76 2009.7
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The growth factor midkine regulates the renin-angiotensin system in mice. Reviewed
Hobo A, Yuzawa Y, Kosugi T, Kato N, Asai N, Sato W, Maruyama S, Ito Y, Kobori H, Ikematsu S, Nishiyama A, Matsuo S, Kadomatsu K.
J Clin Invest. page： 1616-25 2009.6
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Overexpression of calmodulin in pancreatic beta cells induces diabetic nephropathy. Reviewed
Yuzawa Y, Niki I, Kosugi T, Maruyama S, Yoshida F, Takeda M, Tagawa Y, Kaneko Y, Kimura T, Kato N, Yamamoto J, Sato W, Nakagawa T, Matsuo S.
J Am Soc Nephrol. page： 1701-11 2008.9
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Midkine is involved in tubulointerstitial inflammation associated with diabetic nephropathy. Reviewed
Kosugi T, Yuzawa Y, Sato W, Arata-Kawai H, Suzuki N, Kato N, Matsuo S, Kadomatsu K.
Lab Invest. page： 903-13 2007.9
MISC 1
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miR-146a targeted to splenic macrophages prevents sepsis-induced multiple organ injury Reviewed
Funahashi Y, Kato N, Masuda T, Nishio F, Kitai H, Ishimoto T, Kosugi T, Tsuboi N, Matsuda N, Maruyama S, Kadomatsu K
Laboratory investigation; a journal of technical methods and pathology 2019.1
KAKENHI (Grants-in-Aid for Scientific Research) 10
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Grant number：24K11385 2024.4 - 2027.3
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Authorship：Coinvestigator(s)
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aHUS早期診断及び抗補体薬の適応判断に必要な補体機能検査開発
Grant number：22K08349 2022.4 - 2025.3
科学研究費助成事業 基盤研究(C)
加藤 規利, 前田 佳哉輔, 丸山 彰一, 水野 正司, 古橋 和拡, 小杉 智規
Authorship：Principal investigator
Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）
aHUSは血液中ではなく、血管内皮細胞膜上での無秩序な補体活性化が問題であり、単純な採血で評価できないところに検査開発の難しさがある。我々は、2020年より開始したaHUS全国調査研究で登録のあった症例の血漿から、細胞外小胞（Exosomes）を精製し、Exosomes上の補体関連タンパクを測定し、細胞膜上の補体活性を評価する。またex vivoでaHUS患者の血漿と血管内皮細胞株との反応系にエクリズマブを添加することにより、実際に薬剤を投与する前に、治療反応性を見極める。
我々は、非典型溶血性尿毒症症候群(aHUS)の疾患事務局を、2020年より東京大学から引き継ぎ、医療施設からの症例相談を受けるとともに、奈良県立医科大学にて開発されたヒツジ赤血球溶血試験（補体機能検査）や、抗H因子抗体（抗CFH抗体）価を測定するなどして研究、臨床の両面から知見を蓄積してきた。2020年度は62症例の臨床相談を受け、91検体の解析を行った。2021年度は65症例の臨床相談を受け、81検体の解析を行った。そして本研究を開始した2022年度は73症例の相談、85検体の解析を行った。2023年度は10月までに64症例の相談、66検体の解析を行った。
当方で53例のaHUSの診断に至り、うち補体関連遺伝子の病的バリアント保有例は26症例、病的バリアント未検出は20症例、未検査7症例であった。病的バリアント保有割合は57％（26/46）という数字は、過去の報告と同等な値で、概ね妥当な数値と考えられる。
26症例の病的バリアントの内訳は、CFH：9例、C3：12例、CD46：３例、CFI：2例（１例のC3, CD46重複例を含む）であった。世界的にはCFHの病的バリアント保有例の割合が高いが、本邦ではC3、特にC3 I1157Tバリアントの割合が高いことは、既に報告(Clin Exp Nephrol . 2018 Oct;22(5):1088-1099.)があり、同じ傾向であった。
上記の様に、疾患の概要、特に本邦における特徴が明らかになっている。我々は非典型溶血性尿毒症症候群全国調査研究とリンクして、既存のヒツジ赤血球溶血試験のさらなる解析をすすめるとともに、治療法の開発は進んでいるが早期に診断する検査法がない問題点を解決するべく、新規のaHUS診断法を開発している。
aHUSは希少疾患であり、本研究（非典型溶血性尿毒症症候群(aHUS)全国調査研究）は、現在日本で行われているaHUSの最大のコホート研究であると言える。上述のように53症例の診断に寄与してきた実績があり、本年度の症例数も例年と同じ水準~やや多めの数を記録している。aHUSのみならず他のTMA（STEC-HUS, TTP, 二次性TMA）の症例も含まれていることが、本コホート研究の強みである。つまり、aHUSの診断に寄与する検査方法を、他のTMAを引き起こす疾患と比較することができる。
血漿中のC5b-9の値は補体活性化の最終経路を反映するものであり、aHUS症例で上昇するものの、STEC-HUS及びTTP、また二次性TMAの一部でも上昇する結果となった。これは、補体第2経路以外によっても最終的には補体最終経路を活性化するため、aHUSのような補体第2経路の異常な活性化以外の疾患においても、二次的に古典経路、レクチン経路など第2経路以外の経路から補体が活性化してしまえば、C5b-9が上昇してしまうこととなる。一方でC3bに関しては、古典経路、レクチン経路からも生成される補体成分であるが、第２経路の活性化によって血清中のC3が低下することでわかるように、第2経路のみに存在する増幅回路によって、他の経路よりもC3の消費が激しく、それによりC3bの生成が多いことが示唆される。よって最終経路を測定するよりも、第2経路を観察するにはC3bにまつわるコンポーネントを測定するほうが望ましいと考えられた。引き続き症例を重ねてデータを収集し、最終年度での報告につなげたい。
aHUS疾患事務局の活動をベースに、同意の得られた検体を用いて解析を進めていく。名古屋大学医学部腎臓内科のホームページにおいて事務局の活動を報告、案内するとともに、学会等で成果を報告していく。
エクソソームを用いたaHUS診断に関しては、知財取得に務めた上でデータの蓄積をすすめ、解析を行う。
血管内皮細胞を用い、フローサイトメトリーでの解析に関しては、ヒツジ赤血球溶血試験に次ぐ補体機能検査としての可能性を持っており、症例数を増やしたうえで解析を進め、論文化につなげていく予定である。 -
難治性ネフローゼ症候群のエネルギー代謝動態から迫る新たな治療標的の探索
Grant number：22K08308 2022.4 - 2025.3
科学研究費助成事業 基盤研究(C)
前田 佳哉輔, 佐藤 由香, 小杉 智規, 加藤 規利
Authorship：Coinvestigator(s)
進行性ポドサイト障害による難治性ネフローゼ症候群は病態解明と治療標的の探索が課題であり、申請者らは進行性ポドサイト障害のシグナル経路の同定、ポドサイト標的デリバリーシステムの開発を行っており、ネフローゼ症候群において治療抵抗例で解糖系由来のエネルギー産生が低下し、ポドサイト障害を誘導する事を、治療反応例では解糖系由来のエネルギー産生は維持され、障害が抑制される結果を得ている。本課題では、①ポドサイト障害時の解糖系のエネルギー代謝機構の解明、②治療抵抗/反応例のエネルギー代謝ネットワークの比較・解析、③治療抵抗例のエネルギー産生機構に関する液性因子の同定を行い、有効な治療標的の探索をめざす。
持続するポドサイト障害は、糸球体硬化そして慢性腎不全へと進行する慢性腎臓病の共通のメカニズムであり、その病態解明やポドサイトを標的とした治療開発が望まれる。一次性の巣状分節性糸球体硬化症は、原因不明の難治性ネフローゼ症候群で、進行性のポドサイト障害をおこし、真に特異的な治療法がないのが現状である。本研究では、ポドサイト障害時のエネルギー代謝ダイナミクスの点から巣状分節性糸球体硬化症をはじめとする難治性ネフローゼ症候群の病態解明と、臨床情報も合わせた患者の層別化、それから導き出される傷害誘導因子の同定を目的としている。患者血清を使用した実験において、巣状分節性糸球体硬化症の患者血清による刺激は、微小変化型ネフローゼ症候群の患者血清刺激時と比べて有意にヒトポドサイト傷害を誘導した。この傷害性は副腎皮質ステロイド抵抗性（臨床的緩解への至りにくさ）と関係し、病理学的にも分節性病変の程度と正の相関を認めた。これらは血清を使用したin vitroの系が臨床的予後を予測できる可能性を示唆するものである。メタボローム解析による網羅解析においてはエネルギー代謝との関連がみられ、とくに解糖系経路がこの傷害性の差に寄与している結果を得た。ポドサイト特異的解糖系酵素欠損マウスを作成し解析を行ったが、正常時において明らかなタンパク尿は認めていない。
予後不良群とエネルギー代謝動態との関連性が明らかになりつつあり、今後の液性因子同定への患者群の設定についても進めることが可能になっているため。
遺伝子欠損マウスの解析をすすめる。 -
Renal plasma flow (RPF) and accurate GFR equations utilizing metabolomics analysis
Grant number：20H03575 2020.4 - 2023.3
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
Yasuda Yoshinari
Authorship：Coinvestigator(s)
In this study, GFR and RPF were measured, and novel RPF equation was created by using metabolome analysis, which was validated in Japanese patients treated by SGLT2 inhibitor. Among patients with small muscle mass, new GFR equation using psoas muscle index (PMI) in CT images was created and validated in patients with spinal cord injury or spinal cord injury or anorexia nervosa. CKD-EPIcr 2021 equation without race coefficient has been reported, however we revealed that the equation overestimates GFR among Japanese patients and Japanese coefficient of 0.908 was needed. In international collaboration study measuring GFR by inulin clearance, we clarified that CKD-EPIcys2021 could accurately estimate GFR in Japanese and Indians, although they have smaller body muscle mass compared with Caucasians or African Americans.
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Usefulness of Basigin as a novel therapeutic target for diabetic kidney and liver diseases
Grant number：20K08632 2020.4 - 2023.3
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
KOSUGI TOMOKI
Authorship：Coinvestigator(s)
Basigin (Bsg) promotes intracellular transport of monocarboxylic acids. Upon high-fat diet loading, Bsg deficiency ameliorated diabetes and insulin resistance, and reduce renal damage and fatty liver disease. To develop new therapeutic strategies for diabetic kidney disease and fatty liver disease, this study aimed to elucidate the detailed involvements of Bsg in intracellular metabolic mechanisms and to conduct therapeutic experiments with artificial nucleic acids using high-fat diet-loaded mice. In primary cultured cells of liver and renal proximal tubules, intermediate metabolites in the TCA circuit were reduced by 30% to 70% by Bsg inhibition. Systemic administration experiments in high-fat diet-loaded mice showed a trend toward improvement in serological indices in the liver, but it was difficult to conclude that the treatment had a significant effect on diabetes mellitus.
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Novel CaMK4-mediated podocyte-specific therapy in refractory renal disease
Grant number：19K08723 2019.4 - 2022.3
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Maeda Kayaho
Authorship：Coinvestigator(s)
We elucidated the role of CaMK4 in refractory nephrotic syndrome such as focal segmental glomerulosclerosis, and developed podocyte-specific therapy. The findings using podocyte-specific CaMK4-deficient mice showed that CaMK4 in podocytes is involved in podocyte cell death and induces more proteinuria, and podocyte-directed nanoparticles with a CaMK4 inhibitor showed the efficacy compared to administration without nanoparticles.
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Development of a treatment for septic AKI using microRNAs and adipose stem cell-derived exosomes.
Grant number：19K08676 2019.4 - 2022.3
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Noritoshi Kato
Authorship：Principal investigator
Grant amount：\4420000 （ Direct Cost: \3400000 、 Indirect Cost：\1020000 ）
In our previous studies, we have succeeded in suppressing hypercytokinemia and improving survival in sepsis model mice by systemic administration of a plasmid expressing miR-146a, which was mainly taken up by the spleen.
In this study, we focused on the spleen as a target for the treatment of sepsis and investigated the therapeutic effect of local injection into the spleen. We found that most of the nucleic acids after administration were taken up by the spleen, especially by splenic macrophages. While the therapeutic effect was protective against organ damage such as kidney and liver damage, this did not improve the survival rate. Therefore, the target disease and therapeutic miRNAs were changed, and the inhibitory effect on renal fibrosis caused by folic acid nephropathy was examined, and a certain inhibitory effect on fibrosis was confirmed. -
The development of nucleic acid therapeutic against sepsis targeting splenic macrophage
Grant number：18K19562 2018.6 - 2020.3
Grant-in-Aid for Challenging Research (Exploratory)
Yasuda Yoshinari
Authorship：Coinvestigator(s)
We have been involved in nucleic acid therapeutics using miR-146a expression vector for severe sepsis mice model. When introduced miR-146a expression vector with PEI, they are transfected into splenic macrophages and suppress cytokine storm and contribute to improve better survival. This time, we injected mature miR-146a directly into mice spleen. It improved organ damage but did not survival rate. In vitro study, we confirm our artificial nucleic acid suppress cytokine production. Now we are developing better therapeutic platform.
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Investigation of safer methods of therapeutic miRNA and exosomes
Grant number：16K09610 2016.4 - 2019.3
Kato Noritoshi
Authorship：Principal investigator
Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）
We investigated the pathophysiological role of exogenously applied microRNA (miRNA) in sepsis-induced multiple organ injury. In vitro, we tested possible miRNAs which suppressed the production of pro-inflammatory cytokines. Of these, miR-146a displayed the highest suppressive effect. Sepsis was induced in mice via cecal ligation and puncture (CLP) and an intravenous injection of a complex of miR-146a-expressing plasmid and polyethyleneimine. Treatment with this complex significantly decreased the level of serum inflammatory cytokines, attenuated organ injury, and led to increased survival from sepsis. miR-146a-expressing plasmid was abundantly distributed in splenic macrophages. CLP mice treated with miR-146a displayed significantly decreased NF-κB activation in the spleen. The collective results support the conclusion that the induction of miR-146a expression in splenic macrophages prevents excessive inflammation and sepsis-induced multiple organ injury.
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心腎連関における細胞外小胞Exosomesの役割と、心予後予測因子の開発
2014.4 - 2016.3
科学研究費補助金 若手研究(B)
Authorship：Principal investigator
Industrial property rights 1
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EXOSOMES RECOVERY METHOD FOR RENAL DISEASE DIAGNOSIS
Noritoshi Kato