Cell adhesion signalling in acute renal failure

Abstract

Acute renal failure (ARF) remains a severe clinical problem with high mortality. Little progress has been made over the past two decades in preventing renal injury or reducing mortality. This thesis describes the research to investigate cell adhesion alterations during the pathopysiology of both ischemia and toxin-induced ARF. Several key molecules were identified that are involved in cell adhesion and stress signal transduction which contributed to kidney injury, such as ERK and FAK. Other proteins, such as Epac, were found to stabilize cell adhesions thus protecting against renal injury. This research provides a more clear insight into the molecular and cellular mechanisms of ARF-associated cell adhesion alterations and also leads to the development of novel strategies for ARF therapy based on cell adhesion modulation. Indeed, both genetic and pharmacologic means were applied in this thesis to strengthen or stabilize cell adhesions and were ultimately able to reduce ischemia-induced ARF.