Journal
BMC NEPHROLOGY
Volume 16, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s12882-015-0057-x
Keywords
beta 2-microglobulin; Epithelial-mesenchymal transition; Hemochromatosis
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Funding
- Distinguished Researcher Program of Jiangsu Province of China
- Science and Technology Projects of Nanjing [201201089]
- Medical Science and Technology Development Key State Projects of Nanjing [ZKX11177]
- Nature Science Research of Jiangsu Province University [12KJB320002]
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Background: The objective of this study was to investigate the influence of beta 2-microglobulin (beta 2-M) on the epithelial-mesenchymal transition (EMT) in renal tubular epithelial cells. Methods: A human kidney proximal tubular cell line (HK-2) was used as the proximal tubular cell model. HK-2 cells were exposed to different concentrations of beta 2-M (5, 10, 25, and 50 mu M) for up to 24, 48 and 72 h. The effects of beta 2-M on cell morphology were observed by phase contrast microscopy, and the possible associated mechanisms were assessed by immunofluorescence staining, western blot, RNA interference, immunoprecipitation, and induced coupled plasma mass spectroscopy. Results: beta 2-M induced marked morphological alterations in the HK-2 cells, accompanied by the increased expression of extracellular matrix components and alpha-smooth muscle actin (alpha-SMA), vimentin and fibronectin and the reduced expression of E-cadherin. Our results also revealed that beta 2-M could induce the EMT in the HK-2 cells without significant affecting cell viability. Excess beta 2-M in the HK-2 cells led to a decrease in iron and an increase in hypoxia inducible factor-1 alpha (HIF-1 alpha), which induced EMT in the HK-2 cells. Additionally, disrupting the function of the beta 2-M/hemochromatosis (HFE) complex by HFE knockdown was sufficient to reverse beta 2-M-mediated EMT in the HK-2 cells. Conclusion: These findings demonstrate that the activity of beta 2-M is mediated by the beta 2-M/HFE complex, which regulates intracellular iron homeostasis and HIF-1 alpha and ultimately induces EMT in HK2 cells.
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