Different modes of renal proximal tubule regeneration in health and disease.

Tissues are equipped with reasonable strategies for repair and regeneration and the renal proximal tubule (PT) is no exception. New information has become available on the mode of PT regeneration in mammals. Unlike the intestinal epithelium with a high rate of turnover maintained by the stem cell system, the kidney has low turnover under normal physiological conditions. The PT seems to be maintained physiologically by hyperplasia, a regenerating system with self-renewal of mature tubular cells. This mode of regeneration is advantageous for effective replenishment of randomly isolated and eliminated tubular cells by self-renewal of adjacent cells. On the other hand, it has been suggested that dedifferentiation of mature tubular cells plays a role in regeneration after acute kidney injury. Recent studies employing genetic labeling and DNA-labeling techniques have confirmed that the proliferation of preexisting injured mature tubular cells contributes mainly to PT regeneration in ischemic reperfusion injury. This mode of regeneration is beneficial with regard to the rapid reparation of focally injured tubules often induced by ischemic reperfusion injury. What happens, however, when the PT is homogeneously injured with almost no remaining surviving cells Is the PT equipped with another backup regeneration system, e.g., the stem cell system Is it possible that certain types of renal injuries evoke a stem cell response whereas others do not This review focuses on all three possible modes of tissue regeneration (compensatory hyperplasia, dedifferentiation and stem cell system) in mammals and their involvement in PT regeneration in health and disease.