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β2-microglobulin induces epithelial-mesenchymal transition in human renal proximal tubule epithelial cells in vitro

BACKGROUND: The objective of this study was to investigate the influence of β2-microglobulin (β2-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...

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Autores principales: Zhang, Aiqing, Wang, Bin, Yang, Min, Shi, Huimin, Gan, Weihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430907/
https://www.ncbi.nlm.nih.gov/pubmed/25899529
http://dx.doi.org/10.1186/s12882-015-0057-x
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author Zhang, Aiqing
Wang, Bin
Yang, Min
Shi, Huimin
Gan, Weihua
author_facet Zhang, Aiqing
Wang, Bin
Yang, Min
Shi, Huimin
Gan, Weihua
author_sort Zhang, Aiqing
collection PubMed
description BACKGROUND: The objective of this study was to investigate the influence of β2-microglobulin (β2-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 β2-M (5, 10, 25, and 50 μM) for up to 24, 48 and 72 h. The effects of β2-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: β2-M induced marked morphological alterations in the HK-2 cells, accompanied by the increased expression of extracellular matrix components and α-smooth muscle actin (α-SMA), vimentin and fibronectin and the reduced expression of E-cadherin. Our results also revealed that β2-M could induce the EMT in the HK-2 cells without significant affecting cell viability. Excess β2-M in the HK-2 cells led to a decrease in iron and an increase in hypoxia inducible factor-1α (HIF-1α), which induced EMT in the HK-2 cells. Additionally, disrupting the function of the β2-M/hemochromatosis (HFE) complex by HFE knockdown was sufficient to reverse β2-M-mediated EMT in the HK-2 cells. CONCLUSION: These findings demonstrate that the activity of β2-M is mediated by the β2-M/HFE complex, which regulates intracellular iron homeostasis and HIF-1α and ultimately induces EMT in HK2 cells.
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spelling pubmed-44309072015-05-15 β2-microglobulin induces epithelial-mesenchymal transition in human renal proximal tubule epithelial cells in vitro Zhang, Aiqing Wang, Bin Yang, Min Shi, Huimin Gan, Weihua BMC Nephrol Research Article BACKGROUND: The objective of this study was to investigate the influence of β2-microglobulin (β2-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 β2-M (5, 10, 25, and 50 μM) for up to 24, 48 and 72 h. The effects of β2-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: β2-M induced marked morphological alterations in the HK-2 cells, accompanied by the increased expression of extracellular matrix components and α-smooth muscle actin (α-SMA), vimentin and fibronectin and the reduced expression of E-cadherin. Our results also revealed that β2-M could induce the EMT in the HK-2 cells without significant affecting cell viability. Excess β2-M in the HK-2 cells led to a decrease in iron and an increase in hypoxia inducible factor-1α (HIF-1α), which induced EMT in the HK-2 cells. Additionally, disrupting the function of the β2-M/hemochromatosis (HFE) complex by HFE knockdown was sufficient to reverse β2-M-mediated EMT in the HK-2 cells. CONCLUSION: These findings demonstrate that the activity of β2-M is mediated by the β2-M/HFE complex, which regulates intracellular iron homeostasis and HIF-1α and ultimately induces EMT in HK2 cells. BioMed Central 2015-04-23 /pmc/articles/PMC4430907/ /pubmed/25899529 http://dx.doi.org/10.1186/s12882-015-0057-x Text en © Zhang et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zhang, Aiqing
Wang, Bin
Yang, Min
Shi, Huimin
Gan, Weihua
β2-microglobulin induces epithelial-mesenchymal transition in human renal proximal tubule epithelial cells in vitro
title β2-microglobulin induces epithelial-mesenchymal transition in human renal proximal tubule epithelial cells in vitro
title_full β2-microglobulin induces epithelial-mesenchymal transition in human renal proximal tubule epithelial cells in vitro
title_fullStr β2-microglobulin induces epithelial-mesenchymal transition in human renal proximal tubule epithelial cells in vitro
title_full_unstemmed β2-microglobulin induces epithelial-mesenchymal transition in human renal proximal tubule epithelial cells in vitro
title_short β2-microglobulin induces epithelial-mesenchymal transition in human renal proximal tubule epithelial cells in vitro
title_sort β2-microglobulin induces epithelial-mesenchymal transition in human renal proximal tubule epithelial cells in vitro
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430907/
https://www.ncbi.nlm.nih.gov/pubmed/25899529
http://dx.doi.org/10.1186/s12882-015-0057-x
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