title: Kidney Injury Molecule-1 is Elevated in Nephropathy and Mediates Macrophage Activation via the Mapk Signalling Pathway.
abstract: OBJECTIVE
  Kidney injury molecule-1 (KIM-1) is highly expressed in renal tubular cells after injury and is usually regarded as an early biomarker of acute kidney injury(AKI). The aim of this study was to determine the role of KIM-1 in the development of renal tubular injury Methods: Clinical samples, three different animal models and in vitro experiments were utilized to determine the possible mechanism underlying the involvement of KIM-1 in kidney injury.
  
  
  RESULTS
  Both plasma and urinary KIM-1 expression levels were significantly higher in AKI and chronic kidney disease (CKD) patients than in healthy volunteers, and urinary KIM-1 expression was significantly higher in CKD patients than in AKI patients. According to the results of our research involving three different mouse models, KIM-1 expression was significantly increased during the early stage of kidney injury and was persistently elevated in renal fibrosis. Our immunofluorescence staining results indicated that KIM-1-positive tubules were surrounded by macrophage infiltrates in regions of kidney injury. Moreover, our transwell, western blotting and real-time PCR data showed that macrophage migration and phenotype transitions were mediated by KIM-1 through the mitogen-activated protein kinase (MAPK) pathway. MAPK pathway inhibition could significantly reverse the effects of KIM-1 with respect to these macrophage phenotype changes and migration.
  
  
  CONCLUSIONS
  KIM-1 expression was markedly elevated in both acute and chronic kidney injury and may play a pivotal role in macrophage activation via the MAPK pathway in kidney disease.
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.forename: Xinghua
authors.initials: X
authors.lastname: Shao
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xie
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiajing
authors.initials: X
authors.lastname: Che
authors.forename: Minfang
authors.initials: M
authors.lastname: Zhang
authors.forename: Weijia
authors.initials: W
authors.lastname: Xu
authors.forename: Yao
authors.initials: Y
authors.lastname: Xu
authors.forename: Shan
authors.initials: S
authors.lastname: Mou
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Ni
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D005919:Glomerular Filtration Rate; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000032:analysis* / Q000097:blood / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D007093:Imidazoles; D015850:Interleukin-6; D011725:Pyridines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: Acute kidney injury; Chronic kidney disease; Kidney injury molecule-1; MAPK signaling pathway; Macrophage