キシ　セイジ   Seiji Kishi   岸　誠司    所属   川崎医科大学  医学部 臨床医学　腎臓・高血圧内科学    職種   特任准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	KIM-1 mediates fatty acid uptake by renal tubular cells to promote progressive diabetic kidney disease.
掲載誌名	正式名：Cell metabolism 略　 称：Cell Metab ISSNコード：19327420/15504131
掲載区分	国外
巻・号・頁	33(5),pp.1042-1061
著者・共著者	Yutaro Mori, Amrendra K Ajay, Jae-Hyung Chang, Shan Mou, Huiping Zhao, Seiji Kishi, Jiahua Li, Craig R Brooks, Sheng Xiao, Heung-Myong Woo, Venkata S Sabbisetti, Suetonia C Palmer, Pierre Galichon, Li Li, Joel M Henderson, Vijay K Kuchroo, Julie Hawkins, Takaharu Ichimura, Joseph V Bonventre
発行年月	2021/05
概要	Tubulointerstitial abnormalities are predictive of the progression of diabetic kidney disease (DKD), and their targeting may be an effective means for prevention. Proximal tubular (PT) expression of kidney injury molecule (KIM)-1, as well as blood and urinary levels, are increased early in human diabetes and can predict the rate of disease progression. Here, we report that KIM-1 mediates PT uptake of palmitic acid (PA)-bound albumin, leading to enhanced tubule injury with DNA damage, PT cell-cycle arrest, interstitial inflammation and fibrosis, and secondary glomerulosclerosis. Such injury can be ameliorated by genetic ablation of the KIM-1 mucin domain in a high-fat-fed streptozotocin mouse model of DKD. We also identified TW-37 as a small molecule inhibitor of KIM-1-mediated PA-albumin uptake and showed in vivo in a kidney injury model in mice that it ameliorates renal inflammation and fibrosis. Together, our findings support KIM-1 as a new therapeutic target for DKD.
DOI	10.1016/j.cmet.2021.04.004
PMID	33951465