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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2011-2-11
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pubmed:abstractText |
Excessive extracellular matrix (ECM) accumulation is the main feature of chronic renal disease including diabetic nephropathy. Plasminogen activator inhibitor (PAI)-1 is known to play an important role in renal ECM accumulation in part through suppression of plasmin generation and matrix metalloproteinase (MMP) activation. The present study examined the effect of PAI-1 antisense oligodeoxynucleotide (ODN) on fibronectin upregulation and plasmin/MMP suppression in primary mesangial cells cultured under high glucose (HG) or transforming growth factor (TGF)-?1, major mediators of diabetic renal ECM accumulation. Growth arrested and synchronized rat primary mesangial cells were transfected with 1 µM phosphorothioate-modified antisense or control mis-match ODN for 24 hours with cationic liposome and then stimulated with 30 mM D-glucose or 2 ng/ml TGF-?1. PAI-1 or fibronectin protein was measured by Western blot analysis. Plasmin activity was determined using a synthetic fluorometric plasmin substrate and MMP-2 activity analyzed using zymography. HG and TGF-?1 significantly increased PAI-1 and fibronectin protein expression as well as decreased plasmin and MMP-2 activity. Transient transfection of mesangial cells with PAI-1 antisense ODN, but not mis-match ODN, effectively reversed basal as well as HG- and TGF-?1-induced suppression of plasmin and MMP-2 activity. Both basal and upregulated fibronectin secretion were also inhibited by PAI-1 antisense ODN. These data confirm that PAI-1 plays an important role in ECM accumulation in diabetic mesangium through suppression of protease activity and suggest that PAI-1 antisense ODN would be an effective therapeutic strategy for prevention of renal fibrosis including diabetic nephropathy.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-10203363,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-11044203,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-11473641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-12115722,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-12761249,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-12897205,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-13679067,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-14657436,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-1481887,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-15780082,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-15840023,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-16735799,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-17035608,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-18216319,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-1833420,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-18977435,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-19322185,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-19625379,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-19786738,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-19934371,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-2670639,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-7742207,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-8188696,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-8393300,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-9048336,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-9143550,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21311679-9853252
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pubmed:language |
eng
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pubmed:journal |
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pubmed:status |
PubMed-not-MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1226-4512
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
385-90
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pubmed:dateRevised |
2011-7-25
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pubmed:year |
2010
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pubmed:articleTitle |
Plasminogen activator inhibitor-1 antisense oligodeoxynucleotides abrogate mesangial fibronectin accumulation.
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pubmed:affiliation |
Department of Bioinspired Science, Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-752, Korea.
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pubmed:publicationType |
Journal Article
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