Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease

Matsunaga Naoya, Eriko Ikeda, Keisuke Kakimoto, Miyako Watanabe, Naoya Shindo, Akito Tsuruta, Hisako Ikeyama, Kengo Hamamura, Kazuhiro Higashi, Tomohiro Yamashita, Hideaki Kondo, Yuya Yoshida, Masaki Matsuda, Takashi Ogino, Kazutaka Tokushige, Kazufumi Itcho, Yoko Furuichi, Takaharu Nakao, Kaori Yasuda, Atsushi DoiToshiaki Amamoto, Hironori Aramaki, Tsuda Makoto, Kazuhide Inoue, Akio Ojida, Koyanagi Satoru, Shigehiro Ohdo

研究成果: ジャーナルへの寄稿記事

4 引用 (Scopus)

抄録

Chronic kidney disease (CKD) is a global health problem, and novel therapies to treat CKD are urgently needed. Here, we show that inhibition of G0/G1 switch 2 (G0s2) ameliorates renal inflammation in a mouse model of CKD. Renal expression of chemokine (C-C motif) ligand 2 (Ccl2) was increased in response to p65 activation in the kidneys of wild-type 5/6 nephrectomy (5/6Nx) mice. Moreover, 5/6Nx Clk/Clk mice, which carry homozygous mutations in the gene encoding circadian locomotor output cycles kaput (CLOCK), did not exhibit aggravation of apoptosis or induction of F4/80-positive cells. The renal expression of G0s2 in wild-type 5/6Nx mice was important for the transactivation of Ccl2 by p65. These pathologies were ameliorated by G0s2 knockdown. Furthermore, a novel small-molecule inhibitor of G0s2 expression was identified by high-throughput chemical screening, and the inhibitor suppressed renal inflammation in 5/6Nx mice. These findings indicated that G0s2 inhibitors may have applications in the treatment of CKD.

元の言語英語
ページ(範囲)262-273
ページ数12
ジャーナルEBioMedicine
13
DOI
出版物ステータス出版済み - 11 1 2016

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Chronic Renal Insufficiency
Switches
Inflammation
Kidney
Gene encoding
Chemokine CCL2
Pathology
Medical problems
Nephrectomy
Transcriptional Activation
Screening
Chemical activation
Cells
Throughput
Apoptosis
Ligands
Mutation
Molecules
Genes
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

これを引用

Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease. / Naoya, Matsunaga; Ikeda, Eriko; Kakimoto, Keisuke; Watanabe, Miyako; Shindo, Naoya; Tsuruta, Akito; Ikeyama, Hisako; Hamamura, Kengo; Higashi, Kazuhiro; Yamashita, Tomohiro; Kondo, Hideaki; Yoshida, Yuya; Matsuda, Masaki; Ogino, Takashi; Tokushige, Kazutaka; Itcho, Kazufumi; Furuichi, Yoko; Nakao, Takaharu; Yasuda, Kaori; Doi, Atsushi; Amamoto, Toshiaki; Aramaki, Hironori; Makoto, Tsuda; Inoue, Kazuhide; Ojida, Akio; Satoru, Koyanagi; Ohdo, Shigehiro.

:: EBioMedicine, 巻 13, 01.11.2016, p. 262-273.

研究成果: ジャーナルへの寄稿記事

Naoya, M, Ikeda, E, Kakimoto, K, Watanabe, M, Shindo, N, Tsuruta, A, Ikeyama, H, Hamamura, K, Higashi, K, Yamashita, T, Kondo, H, Yoshida, Y, Matsuda, M, Ogino, T, Tokushige, K, Itcho, K, Furuichi, Y, Nakao, T, Yasuda, K, Doi, A, Amamoto, T, Aramaki, H, Makoto, T, Inoue, K, Ojida, A, Satoru, K & Ohdo, S 2016, 'Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease', EBioMedicine, 巻. 13, pp. 262-273. https://doi.org/10.1016/j.ebiom.2016.10.008
Naoya, Matsunaga ; Ikeda, Eriko ; Kakimoto, Keisuke ; Watanabe, Miyako ; Shindo, Naoya ; Tsuruta, Akito ; Ikeyama, Hisako ; Hamamura, Kengo ; Higashi, Kazuhiro ; Yamashita, Tomohiro ; Kondo, Hideaki ; Yoshida, Yuya ; Matsuda, Masaki ; Ogino, Takashi ; Tokushige, Kazutaka ; Itcho, Kazufumi ; Furuichi, Yoko ; Nakao, Takaharu ; Yasuda, Kaori ; Doi, Atsushi ; Amamoto, Toshiaki ; Aramaki, Hironori ; Makoto, Tsuda ; Inoue, Kazuhide ; Ojida, Akio ; Satoru, Koyanagi ; Ohdo, Shigehiro. / Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease. :: EBioMedicine. 2016 ; 巻 13. pp. 262-273.
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AU - Naoya, Matsunaga

AU - Ikeda, Eriko

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AU - Watanabe, Miyako

AU - Shindo, Naoya

AU - Tsuruta, Akito

AU - Ikeyama, Hisako

AU - Hamamura, Kengo

AU - Higashi, Kazuhiro

AU - Yamashita, Tomohiro

AU - Kondo, Hideaki

AU - Yoshida, Yuya

AU - Matsuda, Masaki

AU - Ogino, Takashi

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AU - Itcho, Kazufumi

AU - Furuichi, Yoko

AU - Nakao, Takaharu

AU - Yasuda, Kaori

AU - Doi, Atsushi

AU - Amamoto, Toshiaki

AU - Aramaki, Hironori

AU - Makoto, Tsuda

AU - Inoue, Kazuhide

AU - Ojida, Akio

AU - Satoru, Koyanagi

AU - Ohdo, Shigehiro

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N2 - Chronic kidney disease (CKD) is a global health problem, and novel therapies to treat CKD are urgently needed. Here, we show that inhibition of G0/G1 switch 2 (G0s2) ameliorates renal inflammation in a mouse model of CKD. Renal expression of chemokine (C-C motif) ligand 2 (Ccl2) was increased in response to p65 activation in the kidneys of wild-type 5/6 nephrectomy (5/6Nx) mice. Moreover, 5/6Nx Clk/Clk mice, which carry homozygous mutations in the gene encoding circadian locomotor output cycles kaput (CLOCK), did not exhibit aggravation of apoptosis or induction of F4/80-positive cells. The renal expression of G0s2 in wild-type 5/6Nx mice was important for the transactivation of Ccl2 by p65. These pathologies were ameliorated by G0s2 knockdown. Furthermore, a novel small-molecule inhibitor of G0s2 expression was identified by high-throughput chemical screening, and the inhibitor suppressed renal inflammation in 5/6Nx mice. These findings indicated that G0s2 inhibitors may have applications in the treatment of CKD.

AB - Chronic kidney disease (CKD) is a global health problem, and novel therapies to treat CKD are urgently needed. Here, we show that inhibition of G0/G1 switch 2 (G0s2) ameliorates renal inflammation in a mouse model of CKD. Renal expression of chemokine (C-C motif) ligand 2 (Ccl2) was increased in response to p65 activation in the kidneys of wild-type 5/6 nephrectomy (5/6Nx) mice. Moreover, 5/6Nx Clk/Clk mice, which carry homozygous mutations in the gene encoding circadian locomotor output cycles kaput (CLOCK), did not exhibit aggravation of apoptosis or induction of F4/80-positive cells. The renal expression of G0s2 in wild-type 5/6Nx mice was important for the transactivation of Ccl2 by p65. These pathologies were ameliorated by G0s2 knockdown. Furthermore, a novel small-molecule inhibitor of G0s2 expression was identified by high-throughput chemical screening, and the inhibitor suppressed renal inflammation in 5/6Nx mice. These findings indicated that G0s2 inhibitors may have applications in the treatment of CKD.

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