Truong L D, Sheikh-Hamad D, Chakraborty S, Suki W N
Department of Pathology, Baylor College of Medicine, and The Methodist Hospital, Houston, TX 77030, USA.
Semin Nephrol. 1998 Nov;18(6):641-51.
Distinct patterns of cell proliferation and apoptosis have been recognized for tubular, interstitial, and glomerular cells in chronic obstructive uropathy (OU). In many experimental models of OU, tubular cell apoptosis develops quickly after ureter ligation, peaks between 7 and 24 days postobtruction (about 30-fold of control), and tapers thereafter. Apoptosis initially involves the dilated collecting ducts, but subsequently spreads to other tubules. Tubular cell apoptosis probably accounts for renal tissue loss in OU because a direct correlation between its degree and the decline in dry kidney weight is well-documented. Pronounced tubular cell proliferation occurs shortly after ureter ligation, peaks at about day 6 (60-fold above control), and quickly subsides to baseline. Because the peak of tubular cell proliferation immediately precedes the onset of tubular cell apoptosis, a pathogenetic link may exist between these two processes. Interstitial cell apoptosis occurs with an increasing frequency throughout the course of OU (up to 35-fold above control). Interstitial cell proliferation appears in a bimodal pattern with the early peak coinciding with that of tubular cell proliferation and consisting mostly of fibroblasts, whereas the later peak consists mostly of inflammatory cells. Glomerular cell apoptosis and proliferation are not different from control, which explains, in part, the structural integrity of the glomeruli throughout the disease course. Although the general pathways of cell apoptosis and proliferation are well known, the molecular control of these processes in OU is poorly understood. In addition, whether apoptosis or proliferation of tubular and interstitial cells is differentially regulated remains to be studied. However, several molecules known to be activated or overexpressed in kidney with OU may modulate cell apoptosis and proliferation. The relevant functions of these molecules include induction of apoptosis (angiotensin II, reactive oxygen species, jun-N-terminal kinase, p53), inhibition of the cell cycle (transforming growth factor-beta, p21), inhibition of apoptosis (clusterin, epidermal growth factor, insulin-like growth factor, bcl-2, osteopontin), or promotion of interstitial fibroblast proliferation (platelet-derived growth factor).
在慢性梗阻性尿路病（OU）中，肾小管、肾间质和肾小球细胞的细胞增殖和凋亡模式各不相同。在许多OU实验模型中，输尿管结扎后肾小管细胞凋亡迅速发生，在梗阻后7至24天达到峰值（约为对照组的30倍），此后逐渐减少。凋亡最初涉及扩张的集合管，但随后扩散到其他肾小管。肾小管细胞凋亡可能是OU中肾组织丢失的原因，因为其程度与肾干重下降之间的直接相关性已有充分记录。输尿管结扎后不久会出现明显的肾小管细胞增殖，在第6天左右达到峰值（比对照组高60倍），并迅速降至基线水平。由于肾小管细胞增殖的峰值紧接着肾小管细胞凋亡的开始，这两个过程之间可能存在发病机制上的联系。在OU病程中，肾间质细胞凋亡的频率不断增加（比对照组高35倍）。肾间质细胞增殖呈双峰模式，早期峰值与肾小管细胞增殖的峰值一致，主要由成纤维细胞组成，而后期峰值主要由炎症细胞组成。肾小球细胞凋亡和增殖与对照组无差异，这在一定程度上解释了整个疾病过程中肾小球的结构完整性。虽然细胞凋亡和增殖的一般途径已为人所知，但对OU中这些过程的分子控制了解甚少。此外，肾小管和肾间质细胞的凋亡或增殖是否受到不同调节仍有待研究。然而，一些已知在OU肾脏中被激活或过度表达的分子可能调节细胞凋亡和增殖。这些分子的相关功能包括诱导凋亡（血管紧张素II、活性氧、Jun氨基末端激酶、p53）、抑制细胞周期（转化生长因子-β、p21）、抑制凋亡（簇集素、表皮生长因子、胰岛素样生长因子、bcl-2、骨桥蛋白）或促进肾间质成纤维细胞增殖（血小板衍生生长因子）。
