Kevin T. Bush Hiroyuki Sakurai Tatsuo Tsukamoto Sanjay K. Nigam
Although ischemic acute renal failure (ARF) is likely the result of many different factors, much tubule injury can be traced back to a number of specific lesions that occur at the cellular level in ischemic polarized epithelial cells. At the onset of an ischemic insult, rapid and dramatic biochemical changes in the cellular environment occur, most notably perturbation of the intracellular levels of ATP and free calcium and increases in the levels of free radicals, which lead to alterations in structural and functional cellular components characteristic of renal epithelial cells [1-7]. These alterations include a loss of tight junction integrity, disruption of actin-based microfilaments, and loss of the apical basolateral polarity of epithelial cells. The result is loss of normal renal cell function [7-12].
After acute renal ischemia, the recovery of renal tubule function is critically dependent on reestablishment of the permeability barrier, which is crucial to proper functioning of epithelial tissues such as renal tubules. After ischemic injury the formation of a functional permeability barrier, and thus of functional renal tubules, is critically dependent on the establishment of functional tight junctions. The tight junction is an apically oriented structure that functions as both the "fence" that separates apical and basolateral plasma membrane domains and the major paracellular permeability barrier (gate). It is not yet clear how the kidney restores tight junction structure and function after ischemic injury. In fact, tight junction assembly under normal physiological conditions remains ill-understood; however, utilization of the
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