Preisig P A, Franch H A
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8856, USA.
Semin Nephrol. 1995 Jul;15(4):327-40.
Renal epithelial cells that are part of an intact tubule epithelium divide at a very slow rate. However, in response to physiological signals or pathological processes, their rate of growth can rapidly increase. In these situations, the growth response can be hyperplasic (an increase in cell number) and/or hypertrophic (an increase in cell size). This article reviews our current understanding of the signaling pathways involved in renal epithelial cell hyperplasia and hypertrophy. Hyperplasia involves an initiating mitogenic stimulus, followed by the synthesis of a number of proteins that regulate a cascade of events governing progression through each of the phases of the cell cycle (G1, S, G2, and M phases). Renal epithelial cell hypertrophy can occur by cell cycle-dependent or -independent mechanisms. Cell cycle-dependent hypertrophy involves signals that cause cells to enter the first phase of the cell cycle (G1), but become arrested before leaving this phase. The consequence of these two sequential events is cell growth without DNA replication and, thus, cell hypertrophy. pRB plays a key role is the development of this form of hypertrophy. Cell cycle-independent hypertrophy probably involves inhibition of pH-sensitive lysosomal enzymes, leading to decreased protein degradation, and consequently an increase in cell protein content and cell hypertrophy.
作为完整肾小管上皮一部分的肾上皮细胞分裂速度非常缓慢。然而，在对生理信号或病理过程作出反应时，它们的生长速度会迅速加快。在这些情况下，生长反应可以是增生性的（细胞数量增加）和/或肥大性的（细胞大小增加）。本文综述了我们目前对参与肾上皮细胞增生和肥大的信号通路的理解。增生涉及起始的促有丝分裂刺激，随后合成多种蛋白质，这些蛋白质调节一系列控制细胞周期各阶段（G1、S、G2和M期）进程的事件。肾上皮细胞肥大可通过细胞周期依赖性或非依赖性机制发生。细胞周期依赖性肥大涉及导致细胞进入细胞周期第一阶段（G1）但在离开该阶段之前停滞的信号。这两个连续事件的结果是细胞生长但无DNA复制，从而导致细胞肥大。pRB在这种形式的肥大发展中起关键作用。细胞周期非依赖性肥大可能涉及对pH敏感的溶酶体酶的抑制，导致蛋白质降解减少，从而细胞蛋白质含量增加和细胞肥大。
