Cell survival or death in renal tubular epithelium after ischemia-reperfusion injury

Abstract

A major contributor to the development and progression of ischemia-reperfusion (IR)-induced acute renal failure (ARF) is the loss of functioning tubular epithelial cells by means of various cell deletion or death processes. Although the term "acute tubular necrosis" is still used to describe the pathology of ARF, this is a misnomer because apoptotic cell death, as well as necrosis, occurs [1, 2] along with desquamation and loss of viable epithelial cells [3]. Apoptosis was first described in renal disease in 1987 in an animal model of hydronephrosis [4]. In ARF, with reference to only the death processes, the relative contribution of necrosis or apoptosis possibly depends on the extent of the initiating events. For example, after prolonged total renal ischemia, necrosis or "accidental cell death" occurs from the resultant negation of the cell's energy and protein levels. In apoptosis, the cells use their own energy processes and proteins to die, and often the initiating ischemia is more mild [5]. Finally, despite prolonged ischemia, within the heterogeneous renal cell populations there are those that are more sensitive to ischemia, such as the proximal straight tubule and to some extent the thick ascending limb (TAL) of the loop of Henle. It may be hypothesized that these cells tend to undergo necrosis in comparison with the less sensitive segments that undergo apoptosis. Because apoptosis is gene driven, its identification is important because of the possibility of its modulation via molecular controls. However, despite these new concepts of ARF, patient death remains high, at approximately 30 to 50% of ARF cases. Recovery from ARF depends not only on the replacement or regeneration of cells deleted by death, the theme of many recent studies, but also on protection of cells from death. Both processes are dependent on many of the cellular and molecular controls that have evolved in multicellular organisms to manage normal development, differentiation and growth processes, but that then become involved in the pathogenesis and progression of many renal diseases, including ARF.

Activation of Parenchymal CD47 Promotes Renal Ischemia-Reperfusion Injury

“…21 CD47 ligation by TSP1 regulates cellular apoptotic machinery by modulating Fas signaling 22 and has been linked through Bcl-2 homology 3-only protein 19 kD interacting protein-3 (BNIP3) activation to programmed cell death. 23 We assessed tubular cell apoptosis by terminal deoxynucleotidyl transferasemediated digoxigenin-deoxyuridine nick-end labeling (TUNEL) staining and expression of caspase-3, a transducer of programmed cell death.…”

The NLRP3 Inflammasome Promotes Renal Inflammation and Contributes to CKD

“…10 Cellular contents that are inappropriately released after loss of plasma membrane integrity are endogenous adjuvants or danger-associated molecular patterns (DAMPs). [11][12][13] These DAMPs alert the innate immune system to cellular injury and produce a proinflammatory response to aid the repair of damaged tissues.…”

Hematopoietic Stem Cells Contribute to the Regeneration of Renal Tubules after Renal Ischemia-Reperfusion Injury in Mice

“…I/R injury is characterized by alterations in cell metabolism, inflammation, free radical generation, and apoptosis that result in the detachment of renal tubular cells from the basement membrane and shedding into the urine (14 -16). The S3 segments of the proximal tubules located in the outer stripe of the outer medulla are particularly susceptible to ischemic injury and are primarily responsible for the pathophysiological and clinical presentations of ARF (17)(18)(19). Recovery from ARF requires the replacement or regeneration of lost tubular epithelial cells.…”