Role of translocator protein in renal ischemia reperfusion, renal preservation and acute kidney injury

摘要

Translocator protein (TSPO), formerly known as peripheral-type benzodiazepine receptor (PBR), has been described in several tissues and characterized as one of the main elements of steroidogenesis. However, TSPO is also involved in other pathways and cell functions, such as apoptosis regulation, protein import, membrane biogenesis, cell cycle regulation, oxygen homeostasis and mitochondrial membrane fluidity regulation. In the kidney, TSPO is normally located in the distal parts of the nephron from the thick ascending limb of the loop of Henle to the medullary collecting ducts. However when the kidney is submitted to a stress such as ischemia reperfusion injury there is a defined change in TSPO expression towards more proximal areas of the nephron, and the protein can be detected as high as proximal tubular cells and the Bowman Capsule. As the injury persists, TSPO is also located in invading mononucleated cells, in a pattern reproducing invasion by CD4+ helper Tcells, and in the damaged vessels where TSPO is expressed both in endothelial and smooth muscle cells. Herein we review the potential use of TSPO-directed treatment for ischemia reperfusion injury, particularly regarding pre-conditioning of the organ. We also detail the relationship of proximal TSPO staining with the intensity of the injury, particularly the implication of monomeric (18 kDa) TSPO and its role in hypoxiareoxygenation and apoptosis prevention. The potential implications of the protein with regeneration processes activated in response to injury and their relation with embryogenesis pathways are discussed.