CELLULAR MECHANISMS OF TUBULE HYPERTROPHY AND HYPERPLASIA IN RENAL INJURY

Tubular cells can either unergo hyperplasia or hypertrophy, two totally different growth responses. Hyperplasia with mitogenesis of tubular cells plays a central role in the regeneration of functional tubular epithelium subsequent to acute tubular necrosis. Several growth factors acting in concert are involved in this proliferative response of tubular cells. The molecular mechanisms how mitogenic signals are transduced to the nucleus are relatively well characterized. Complex oscillation patterns of cell cycle-associated proteins like cyclins and various kinases are pivotal for the progression of quiescent tubular cells through mitosis. In contrast to the mitogenic growth response of regenerating tubular cells, cellular hypertrophy is less well understood. Hypertrophic cells are arrested in the G(1)-phase of the cell cycle and increase their size, protein and RNA content, but do normally not replicate their DNA. Such an enlargement of tubular cells often occurs in more chronic situations of renal damage in which remnant nephrons adapt their function to the increasing need. However, evidence exists that hypertrophic tubules are finally joined into the process of maladaptation of renal function leading to tubular atrophy, interstitial scarring, and progression of renal disease. It appears that transforming growth factor-beta is involved in the hypertrophy of tubular cells. The present review will address more recent progress in understanding the mechanism of tubular growth at a cellular level. A better knowledge of the molecular factors may ultimately lead to therapeutic strategies preventing the progression of renal and speeding up renal recovery after acute renal failure.