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Article

Advanced glycation end products induce glomerular endothelial cell hyperpermeability by upregulating matrix metalloproteinase activity

  • Authors:
    • Pengli Luo
    • Hui Peng
    • Canming Li
    • Zengchun Ye
    • Hua  Tang
    • Ying Tang
    • Cailian Chen
    • Tanqi Lou
  • View Affiliations / Copyright

    Affiliations: Department of Nephrology, Affiliated Hospital of Qinghai University, Xining, Qinghai 810001, P.R. China, Department of Nephrology, The Third Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510660, P.R. China, Department of Nephrology, The Second Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510000, P.R. China
  • Pages: 4447-4453
    |
    Published online on: January 29, 2015
       https://doi.org/10.3892/mmr.2015.3269
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Abstract

The present study aimed to investigate the effects of advanced glycation end‑products (AGEs) on the permeability of glomerular endothelial cells (GEnCs) and determine whether enhanced permeability was due to degradation of tight junction (TJ) complexes by matrix metalloproteinases (MMPs). Cultured monolayers of GEnCs were exposed to AGEs at different doses and treatment durations in the presence or absence of the organic MMP‑2/9 inhibitor (2R)‑2‑((4‑biphenyl sulfony‑l)amino)‑3‑phenylproprionic acid) (BiPs). Expression of the TJ proteins occludin and claudin‑5 was determined by western blot analysis and immunofluorescence, while the permeability of the GEnCs was measured using transendothelial electrical resistance and by diffusion of 4 kDa fluorescein isothiocyanate (FITC)‑dextran. The activities of MMP‑2 and MMP‑9 were assayed using gelatin zymography. The results indicated that AGE‑treated cultures significantly reduced occludin and claudin‑5 immunoreactivity. Similarly, the surface expression of these proteins was significantly reduced and rows of TJs which normally connect endothelial cells became discontinuous or fractured following AGE exposure. Disruption of TJs was accompanied by significantly reduced transendothelial resistance and hyperpermeability to FITC‑dextran. Treatment with AGEs evoked a dose‑ and time‑dependent upregulation of MMP‑2 and MMP‑9. However, co‑administration of AGEs and BiPS, an inhibitor of MMP‑2/MMP‑9, inhibited the downregulation of occludin and claudin‑5, with a concomitant reversal of GEnC monolayer hyperpermeability. In conclusion, AGEs promoted glomerular hyperpermeability in vitro by the MMP‑mediated disruption of TJs. Chronic elevation of endothelial cell AGEs in diabetes mellitus may contribute to glomerular hyperpermeability by inducing the overexpression of MMPs, which degrade TJs, leading to proteinuria.
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Copy and paste a formatted citation
Spandidos Publications style
Luo P, Peng H, Li C, Ye Z, Tang H, Tang Y, Chen C and Lou T: Advanced glycation end products induce glomerular endothelial cell hyperpermeability by upregulating matrix metalloproteinase activity. Mol Med Rep 11: 4447-4453, 2015.
APA
Luo, P., Peng, H., Li, C., Ye, Z., Tang, H., Tang, Y. ... Lou, T. (2015). Advanced glycation end products induce glomerular endothelial cell hyperpermeability by upregulating matrix metalloproteinase activity. Molecular Medicine Reports, 11, 4447-4453. https://doi.org/10.3892/mmr.2015.3269
MLA
Luo, P., Peng, H., Li, C., Ye, Z., Tang, H., Tang, Y., Chen, C., Lou, T."Advanced glycation end products induce glomerular endothelial cell hyperpermeability by upregulating matrix metalloproteinase activity". Molecular Medicine Reports 11.6 (2015): 4447-4453.
Chicago
Luo, P., Peng, H., Li, C., Ye, Z., Tang, H., Tang, Y., Chen, C., Lou, T."Advanced glycation end products induce glomerular endothelial cell hyperpermeability by upregulating matrix metalloproteinase activity". Molecular Medicine Reports 11, no. 6 (2015): 4447-4453. https://doi.org/10.3892/mmr.2015.3269
Copy and paste a formatted citation
x
Spandidos Publications style
Luo P, Peng H, Li C, Ye Z, Tang H, Tang Y, Chen C and Lou T: Advanced glycation end products induce glomerular endothelial cell hyperpermeability by upregulating matrix metalloproteinase activity. Mol Med Rep 11: 4447-4453, 2015.
APA
Luo, P., Peng, H., Li, C., Ye, Z., Tang, H., Tang, Y. ... Lou, T. (2015). Advanced glycation end products induce glomerular endothelial cell hyperpermeability by upregulating matrix metalloproteinase activity. Molecular Medicine Reports, 11, 4447-4453. https://doi.org/10.3892/mmr.2015.3269
MLA
Luo, P., Peng, H., Li, C., Ye, Z., Tang, H., Tang, Y., Chen, C., Lou, T."Advanced glycation end products induce glomerular endothelial cell hyperpermeability by upregulating matrix metalloproteinase activity". Molecular Medicine Reports 11.6 (2015): 4447-4453.
Chicago
Luo, P., Peng, H., Li, C., Ye, Z., Tang, H., Tang, Y., Chen, C., Lou, T."Advanced glycation end products induce glomerular endothelial cell hyperpermeability by upregulating matrix metalloproteinase activity". Molecular Medicine Reports 11, no. 6 (2015): 4447-4453. https://doi.org/10.3892/mmr.2015.3269
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