title: Identification of a signal transduction pathway that regulates MMP-9 mRNA expression in glomerular injury.
abstract: 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.
authors.affiliation: Medizinische Poliklinik, Ludwig-Maximilians-Universität, München, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: von Lüttichau
authors.forename: Roghieh
authors.initials: R
authors.lastname: Djafarzadeh
authors.forename: Anna
authors.initials: A
authors.lastname: Henger
authors.forename: Clemens D
authors.initials: CD
authors.lastname: Cohen
authors.forename: Anke
authors.initials: A
authors.lastname: Mojaat
authors.forename: Marianne
authors.initials: M
authors.lastname: Jochum
authors.forename: Christian
authors.initials: C
authors.lastname: Ries
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Nelson
authors.forename: Matthias
authors.initials: M
authors.lastname: Kretzler
mesh_terms: 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
chemical_list: 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