In Vivo modulation of integrin linked kinase using transgenic mice

El-Aouni, Chiraz (2006): In Vivo modulation of integrin linked kinase using transgenic mice. Dissertation, LMU München: Fakultät für Biologie

Abstract

Alterations in glomerular podocyte cell-cell and cell-matrix contacts are key events in progressive glomerular failure. Integrin-linked kinase (ILK) has been implicated in podocyte cell matrix interaction and is induced in proteinuria. To evaluate ILK function in vivo, mice with a Cre-mediated podocyte-specific ILK inactivation were generated. These animals appeared normal at birth, but developed progressive focal segmental glomerulosclerosis and died in terminal renal failure. The first ultrastructural lesion seen at onset of albuminuria are glomerular basement membrane (GBM) alterations with a significant increase in true harmonic mean GBM thickness. Podocyte foot processes effacement and loss of slit diaphragm followed with progression to unselective proteinuria. No significant reduction of slit-membrane molecules (podocin and nephrin), key GBM components (fibronectin, laminins and collagen IV isoforms) or podocyte integrins could be observed at onset of proteinuria. However, alpha3-integrins were relocalized into a granular pattern along the GBM, consistent with altered integrin mediated matrix assembly in ILK-deficient podocytes. As the increased GBM thickness precedes structural podocyte lesions and key components of the GBM were expressed at comparable levels to controls, our data imply an essential role of ILK for the close interconnection of GBM structure and podocyte function.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Podocyte, cell-matrix interactions, transgenic mouse
• Themengebiete: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie ; 500 Naturwissenschaften und Mathematik
• Fakultäten: Fakultät für Biologie
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 22. September 2006
• 1. Bericht­erstatter:in: Böttger, Angelika