@article{a3a6e8a213ad41989df24e69d3085249,
title = "Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease",
abstract = "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.",
author = "Naoya Matsunaga and Eriko Ikeda and Keisuke Kakimoto and Miyako Watanabe and Naoya Shindo and Akito Tsuruta and Hisako Ikeyama and Kengo Hamamura and Kazuhiro Higashi and Tomohiro Yamashita and Hideaki Kondo and Yuya Yoshida and Masaki Matsuda and Takashi Ogino and Kazutaka Tokushige and Kazufumi Itcho and Yoko Furuichi and Takaharu Nakao and Kaori Yasuda and Atsushi Doi and Toshiaki Amamoto and Hironori Aramaki and Makoto Tsuda and Kazuhide Inoue and Akio Ojida and Satoru Koyanagi and Shigehiro Ohdo",
note = "Funding Information: This study was supported in part by Grants-in-Aid for Scientific Research (A; 25253038 , 16H02636 ; S. Ohdo), for Scientific Research on Innovative Areas ( 25136716 ; S. Ohdo), and for Challenging Exploratory Research ( 25670079 ; S. Ohdo); The Uehara Memorial Foundation and Scientific Research (C; 24590196 , 15K08098 ; N. Matsunaga); and a Grant-in-Aid for JSPS Fellows ( 25-4175 ; K. Hamamura) from the Japan Society for the Promotion of Science (JSPS) and the Fukuoka Foundation for Sound Health. This work was also supported by the Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science and Technology, Japan. We would like to thank the Research Support Center, Graduate School of Medical Sciences, Kyushu University for technical support. Publisher Copyright: {\textcopyright} 2016 The Authors",
year = "2016",
month = nov,
day = "1",
doi = "10.1016/j.ebiom.2016.10.008",
language = "English",
volume = "13",
pages = "262--273",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",
}