The elucidation of the molecular and cellular mechanisms of ischemic ARF very important in finding new strategies to reduce or prevent renal injury. FAK is an important FA protein with tyrosine... Show moreThe elucidation of the molecular and cellular mechanisms of ischemic ARF very important in finding new strategies to reduce or prevent renal injury. FAK is an important FA protein with tyrosine kinase and scaffolding function. The general goal of this thesis was to investigate the role of FAK during I/R. Using a unilateral renal I/R rat model, we show the presence of tyrosine phosphorylated FAs in vivo and disruption of FAs and the F-actin network after ischemia and rebuild during reperfusion. FAK phosphorylation occured on different tyrosine residues during the reperfusion implicating a role of FAK. ERK is known to be involved in FA signaling. We studied the role of ERK signaling pathway during I/R in vivo using the inhibitor U0126. Inhibition prevented the changes in FA protein phosphorylation after ischemia and diminished injury. We used an inducible proximal tubule cell specific FAK knockout model to investigate the role of FAK in I/R. We show that FAK knockout mice are less susceptible to I/R injury compared to their wildtype littermates. Furthermore we studied FAK signaling under normal and ATP depletion in vitro. FAK deleted renal cells show no differences in morphology. However FAK knockout cells have increased FAs, aberrant stress fibers and impaired spreading. During recovery from ATP depletion, FAK deleted cells show impaired recovery of FAs and stress fibers. Show less
