Identification of a signal transduction pathway that regulates MMP-9 mRNA expression in glomerular injury.
Podocytes contribute to the filtration barrier within the kidney. The integrin-linked kinase (ILK) plays an important role in podocyte adhesion to the glomerular basement membrane, signal transduction and phenotype regulation. We demonstrate that ILK activity is also associated with upregulation of matrix metalloproteinase-9 (MMP-9) mRNA levels during podocyte stress. A synthetic ILK inhibitor blocked MMP-9 mRNA upregulation but showed no effect on TIMP-1 or MMP-2 mRNA expression. Interestingly, a corresponding increase in MMP-9 secretion was not observed, suggesting that MMP-9 mRNA production in podocytes is regulated via ILK, whereas additional signaling pathways may mediate the post-transcriptional regulation of MMP-9.
von Lüttichau
Irene
I
Medizinische Poliklinik, Ludwig-Maximilians-Universität, München, Germany.
Djafarzadeh
Roghieh
R
Henger
Anna
A
Cohen
Clemens D
CD
Mojaat
Anke
A
Jochum
Marianne
M
Ries
Christian
C
Nelson
Peter J
PJ
Kretzler
Matthias
M
D001485:Basement Membrane; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000201:enzymology* / Q000293:injuries; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000099200:Scaffold Protein ILK
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D000099200:Scaffold Protein ILK