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Increased expression of neutrophil gelatinase-associated lipocalin receptor by interleukin-1β in human mesangial cells via MAPK/ERK activation

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Neutrophil gelatinase-associated lipocalin (NGAL), one of the most promising next-generation biomarkers in clinical nephrology, has received extensive attention. However, the basic role of its receptor (NGALR) remains unclear. Here, we have assessed the expression pattern of NGALR in injured glomeruli and explored the possible mechanism of the NGALR involvement in inflammation in human mesangial cells (HMC). The expression pattern of NGALR was detected by immunohistochemistry in biopsy samples of 93 glomerulonephritis patients and healthy controls, and the regulation of NGALR by the proinflammatory cytokines, TGF-β1, TNF-α and IL-1β in HMC was analyzed by real-time PCR and Western blotting. NGALR was found to be expressed in glomeruli. Its expression was significantly higher in acute proliferative glomerulonephritis and lupus nephritis than that in other types of glomerulonephritis or healthy kidney tissues. In in┬ávitro experiments, both mRNA and protein levels of NGALR were dramatically induced by treatment of IL-1β, whereas TGF-β1 or TNF-α did not have the same effect. Furthermore, it was shown that the IL-1β-induced NGALR expression is mediated via the MAPK/ERK signaling pathway by using pharmacological inhibitors. Interestingly, the basal mRNA levels of NGAL detected in HMC, could be induced by IL-1β. However, NGAL protein could not be detected, even with IL-1β treatment. The ability of HMC to express NGAL protein was ascertained by exogenous administration of NGAL. In conclusion, the data show that NGALR is differentially expressed in human glomerular disease and is significantly up-regulated by Il-1β in HMC via MAPK/ERK activation. Furthermore, exogenous NGAL can be uptaken into HMC.
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Document Type: Research Article

Affiliations: 1: Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, P.R. China 2: Department of Pathology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, P.R. China

Publication date: January 1, 2011

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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