Ischemia/reperfusion injury is the most common cause of acute renal failure. Despite advances in supportive treatments such as dialysis, severe acute renal failure remains a major cause of death and has no specific therapies.

In a paper appearing online on November 17 in advance of print publication of the December issue of the Journal of Clinical Investigation, Manoocher Soleimani and colleagues from University of Cincinnati define the early pathways activated by ischemic injury. The authors find that a protein called thrombospondin (TSP-1) can cause severe kidney failure when normal blood flow is disrupted.

TSP-1, known for its ability to prevent angiogenesis and promote death of cancerous cells, is also the molecule with the highest induction level at 3 hours of reperfusion injury in rodent kidneys subjected to ischemia/reperfusion. The predominant sites of expression of TSP-1 are the injured proximal tubules, where TSP-1 colocalizes with activated caspase-3. Cultured kidney cells exposed to TSP-1 also demonstrated signs of programmed cell death-induced damage. Additionally, mice lacking TSP-1 were protected against ischemic injury-induced renal failure and tubular damage. Thus, TSP-1 is a novel mediator of ischemic damage in the kidney and may be a target for drugs that will reduce the risk of kidney failure in humans.

TITLE: Identification of Thrombospondin 1 (TSP-1) as a novel mediator of cell injury in kidney ischemia

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Stacie Bloom
press_releasesthe-jci
Journal of Clinical Investigation
jci
December 2005

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