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学科主题临床医学
KIM-1-mediated phagocytosis reduces acute injury to the kidney
Yang, Li1,2; Brooks, Craig R.1; Xiao, Sheng3; Sabbisetti, Venkata1; Yeung, Melissa Y.1,4; Hsiao, Li-Li1; Ichimura, Takaharu1; Kuchroo, Vijay3; Bonventre, Joseph V.1,5
刊名JOURNAL OF CLINICAL INVESTIGATION
2015-04-01
DOI10.1172/JCI75417
125期:4页:1620-1636
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, Research & Experimental
资助者NIH ; National Natural Science Foundation of China ; NIH ; National Natural Science Foundation of China
研究领域[WOS]Research & Experimental Medicine
关键词[WOS]ACUTE-RENAL-FAILURE ; ISCHEMIA-REPERFUSION INJURY ; INNATE IMMUNE-RESPONSE ; T-CELL IG ; EPITHELIAL-CELLS ; APOPTOTIC CELLS ; B-CELLS ; ISCHEMIA/REPERFUSION INJURY ; URINARY BIOMARKER ; MOLECULE-1 KIM-1
英文摘要

Kidney injury molecule 1 (KIM-1, also known as TIM-1) is markedly upregulated in the proximal tubule after injury and is maladaptive when chronically expressed. Here, we determined that early in the injury process, however, KIM-1 expression is antiinflammatory due to its mediation of phagocytic processes in tubule cells. Using various models of acute kidney injury (AKI) and mice expressing mutant forms of KIM-1, we demonstrated a mucin domain-dependent protective effect of epithelial KIM-1 expression that involves downregulation of innate immunity. Deletion of the mucin domain markedly impaired KIM-1-mediated phagocytic function, resulting in increased proinflammatory cytokine production, decreased antiinflammatory growth factor secretion by proximal epithelial cells, and a subsequent increase in tissue macrophages. Mice expressing KIM-1(Delta mucin) had greater functional impairment, inflammatory responses, and mortality in response to ischemia- and cisplatin-induced AKI. Compared with primary renal proximal tubule cells isolated from KIM-1(Delta mucin) mice, those from WT mice had reduced proinflammatory cytokine secretion and impaired macrophage activation. The antiinflammatory effect of KIM-1 expression was due to the interaction of KIM-1 with p85 and subsequent PI3K-dependent downmodulation of NF-kappa B. Hence, KIM-1-mediated epithelial cell phagocytosis of apoptotic cells protects the kidney after acute injury by downregulating innate immunity and inflammation.

语种英语
所属项目编号DK39773 ; DK72381 ; DK088418 ; 81270777
资助者NIH ; National Natural Science Foundation of China ; NIH ; National Natural Science Foundation of China
WOS记录号WOS:000352248600026
引用统计
被引频次:48[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59651
专题北京大学第一临床医学院_肾脏内科
作者单位1.Harvard Stem Cell Inst, Cambridge, MA USA
2.Harvard Univ, Brigham & Womens Hosp, Sch Med, Renal Div,Dept Med, Boston, MA 02115 USA
3.Peking Univ, Hosp 1, Key Lab Renal Dis, Div Renal,Minist Hlth China,Dept Med,Inst Nephrol, Beijing 100034, Peoples R China
4.Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA
5.Harvard Univ, Brigham & Womens Hosp, Sch Med, Transplantat Res Ctr,Renal Div, Boston, MA 02115 USA
推荐引用方式
GB/T 7714
Yang, Li,Brooks, Craig R.,Xiao, Sheng,et al. KIM-1-mediated phagocytosis reduces acute injury to the kidney[J]. JOURNAL OF CLINICAL INVESTIGATION,2015,125(4):1620-1636.
APA Yang, Li.,Brooks, Craig R..,Xiao, Sheng.,Sabbisetti, Venkata.,Yeung, Melissa Y..,...&Bonventre, Joseph V..(2015).KIM-1-mediated phagocytosis reduces acute injury to the kidney.JOURNAL OF CLINICAL INVESTIGATION,125(4),1620-1636.
MLA Yang, Li,et al."KIM-1-mediated phagocytosis reduces acute injury to the kidney".JOURNAL OF CLINICAL INVESTIGATION 125.4(2015):1620-1636.
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