Thrombin stimulates MMP-9 mRNA expression through AP-1 pathway in human mesangial cells.
OBJECTIVE
To investigate the thrombin mediated induction of gelatinase B (MMP-9) in mesangial cells (MC) and the underlying role of activator protein-1 (AP-1).


METHODS
Cultured human mesangial cells were exposed to thrombin in the presence or absence of hirudin, curcumin, and c-fos antisense or sense oligonucleotides. Northern hybridization was employed to assess MMP-9 mRNA expression, and electrophoretic mobility shift assay (EMSA) for AP-1 DNA binding activity.


RESULTS
The levels of MMP-9 mRNA in the cell treated with different doses of thrombin (500, 1500, and 4500 u/L, respectively) were 1.1, 3.3, and 4.8 times higher than that in the control, respectively. There was also an increase in AP-1 binding activity (3.5, 5.9, and 7.1 fold than that of the control) in accordance with MMP-9 mRNA levels in the presence of thrombin. Hirudin, curcumin, and c-fos antisense oligonucleotides could block thrombin-induced expression of MMP-9 mRNA as well as AP-1 binding activity.


CONCLUSIONS
Thrombin is a potent stimulator of MMP-9 gene expression in human mesangial cells, and the underlying intracellular events are mediated, at least partly, by AP-1 pathway.
Liu
W H
WH
Department of Nephrology, Fourth Affiliated Hospital of Hebei Medical College, Shijiazhuang 050011, China. Wenhuliu@hotmail.com
Chen
X M
XM
Fu
B
B
D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000502:physiology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006629:Hirudins / Q000494:pharmacology; D018398:Homeodomain Proteins; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D013917:Thrombin / Q000494:pharmacology*
C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D006629:Hirudins; D018398:Homeodomain Proteins; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D013917:Thrombin; D020780:Matrix Metalloproteinase 9; D051818:Replication Protein C; D003474:Curcumin