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 |
| 巻 | 13 |
| DOI | |
| 出版物ステータス | 出版済み - 11 1 2016 |
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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
}
TY - JOUR
T1 - Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease
AU - Naoya, Matsunaga
AU - Ikeda, Eriko
AU - Kakimoto, Keisuke
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
AU - Tokushige, Kazutaka
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
PY - 2016/11/1
Y1 - 2016/11/1
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.
UR - http://www.scopus.com/inward/record.url?scp=85006052082&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85006052082&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2016.10.008
DO - 10.1016/j.ebiom.2016.10.008
M3 - Article
VL - 13
SP - 262
EP - 273
JO - EBioMedicine
JF - EBioMedicine
SN - 2352-3964
ER -