title: Kidney injury molecule-1 expression in IgA nephropathy and its correlation with hypoxia and tubulointerstitial inflammation.
abstract: Tubulointerstitial injury plays an important role in the development and progression of chronic kidney disease (CKD). Kidney injury molecule (KIM)-1 is induced in damaged proximal tubules in both acute renal injury and CKD. However, the dynamics of KIM-1 in CKD and effects of KIM-1 expression on disease progression are unknown. Here, we aimed to determine the associations between tubular KIM-1 expression levels, renal function, and inflammation in CKD. The relationships between levels of KIM-1 and clinicopathological parameters were analyzed in patients with progressive and nonprogressive IgA nephropathy. KIM-1 expression was increased in patients with IgA nephropathy, and its expression was significantly correlated with the decrease of renal function. KIM-1 was particularly evident at the site with reduced capillary density, and KIM-1-positive tubules were surrounded by infiltrates of inflammatory cells. Using in vitro cell models, we showed that cellular stressors, including hypoxia, induced KIM-1 expression. KIM-1-expressing cells produced more chemokines/cytokines when cultured under hypoxic conditions. Furthermore, we showed that tubular cells with KIM-1 expression can regulate the immune response of inflammatory cells through the secretion of chemotactic factors. These data suggest that KIM-1-expressing epithelial cells may play a role in the pathogenesis of tubulointerstitial inflammation during chronic renal injury through the secretion of chemokines/cytokines.
authors: Renal Division, Dept. of Medicine, Peking Univ. First Hospital, and Institute of Nephrology, Peking Univ., Beijing 100034, People's Republic of China. li.yang@bjmu.edu.cn.
authors: Qiongzhen
authors: Q
authors: Lin
authors: Ying
authors: Y
authors: Chen
authors: Jicheng
authors: J
authors: Lv
authors: Hong
authors: H
authors: Zhang
authors: Jiawei
authors: J
authors: Tang
authors: Lakshman
authors: L
authors: Gunaratnam
authors: Xiaomei
authors: X
authors: Li
authors: Li
authors: L
authors: Yang
mesh_terms: D000328:Adult; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005922:Glomerulonephritis, IGA / Q000473:pathology / Q000503:physiopathology*; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis; D007668:Kidney / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D011991:Receptors, Virus / Q000096:biosynthesis*; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D014409:Tumor Necrosis Factor-alpha
keywords: IgA nephropathy; hypoxia; kidney injury molecule-1; tubulointerstitial inflammation