Sirt1 activation prevents anti-Thy 1.1 mesangial proliferative glomerulonephritis in the rat through the Nrf2/ARE pathway

Mesangial proliferative glomerulonephritis (MsPGN) is characterized by glomerular mesangial cells proliferation and extracellular matrix deposition in mesangial area, which develop into glomerulosclerosis. Both silent information regulator 2-related protein 1 (Sirt1) and nuclear factor erythroid 2-r...

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Bibliographic Details
Published in:European journal of pharmacology 2018-08, Vol.832, p.138-144
Main Authors: Huang, Kaipeng, Li, Ruiming, Wei, Wentao
Format: Article
Language:English
Subjects:
Animals
Antioxidants - metabolism
Enzyme Activation - drug effects
Glomerulonephritis - enzymology
Glomerulonephritis - pathology
Glomerulonephritis - prevention & control
Male
Mesangial Cells - drug effects
Mesangial Cells - pathology
MsPGN
NF-E2-Related Factor 2 - metabolism
Nrf2-ARE anti-oxidative pathway
Rats
Rats, Sprague-Dawley
Rats, Wistar
Response Elements - drug effects
Sirt1
Sirtuin 1 - metabolism
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Summary:Mesangial proliferative glomerulonephritis (MsPGN) is characterized by glomerular mesangial cells proliferation and extracellular matrix deposition in mesangial area, which develop into glomerulosclerosis. Both silent information regulator 2-related protein 1 (Sirt1) and nuclear factor erythroid 2-related factor 2/anti-oxidant response element (Nrf2/ARE) pathway had remarkable renoprotective effects. However, whether Sirt1 and Nrf2/ARE pathway can regulate the pathological process of MsPGN remains unknown. Here, we found that Sirt1 activation by SRT1720 decreased mesangial hypercellularity and mesangial matrix areas, reduced renal Col4 and α-SMA expressions, lowered 24 h proteinuria, and eventually reduced FN and TGF-β1 expressions in rats received anti-Thy 1.1 IgG. Further study showed that SRT1720 markedly enhanced the activity of Nrf2/ARE pathway including promoting the nuclear content and ARE-binding ability of Nrf2, elevating the protein levels of HO-1 and SOD1, two target genes of Nrf2, which eventually increased total SOD activity and decreased malondialdehyde level in the kidney tissues of experimental anti-Thy 1.1 MsPGN rats. Taken together, Sirt1 prevented the pathological process of experimental anti-Thy 1.1 MsPGN through promoting the activation of Nrf2/ARE pathway, which warrants further elucidation. Sirt1 might be a potential therapeutic target for treating MsPGN.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2018.05.017