Grantham J J
Department of Medicine, University of Kansas Medical Center, Kansas City 66160, USA.
Am J Kidney Dis. 1996 Dec;28(6):788-803. doi: 10.1016/s0272-6386(96)90378-9.
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in at least three different genes: PKD1, PKD2, and PKD3. ADPKD1 is an inherited disorder that has led to the discovery of a novel protein, polycystin. Polycystin, a 460 kd protein with a host of domains implicating a potential role in cell-cell and cell-matrix regulation, is encoded by a 52 kb gene with a 14 kb mRNA. The PKD2 protein is also large (110 kd) and is thought to interact with polycystin. ADPKD1 is caused by mutated DNA that encodes an abnormal form of polycystin. Polycystin appears to have a normal role in the differentiation of epithelial cells, and when defective, these cells fail to maturate fully. These incompletely differentiated cells proliferate abnormally and express altered amounts of otherwise normal electrolyte transport proteins that result in excessive secretion of solute and fluid into the cysts. The proliferation of the cells and the associated apoptosis, and the secretion of the fluid into the cysts created by the enlarging tubule segments appear to be regulated by growth factors, hormones, and cytokines that can alter the extent to which the disease is clinically expressed among individuals. The formation of the cysts is associated with complex changes in the extracellular matrix of the kidneys and other organs that may be directly or indirectly tied to mutated polycystin. The summation of these pathogenetic elements leads to renal interstitial infiltration, with monocytes, macrophages, and fibroblasts culminating in fibrosis and progressive loss of renal function. The modem understanding of cyst pathogenesis opens opportunities to develop treatments that may diminish or halt altogether the progression of this disease.
常染色体显性多囊肾病（ADPKD）由至少三种不同基因的突变引起：PKD1、PKD2和PKD3。ADPKD1是一种遗传性疾病，它促使人们发现了一种新蛋白质——多囊蛋白。多囊蛋白是一种460kd的蛋白质，具有许多结构域，暗示其在细胞间和细胞与基质调节中可能发挥作用，由一个52kb的基因编码，mRNA为14kb。PKD2蛋白也很大（110kd），被认为与多囊蛋白相互作用。ADPKD1是由编码异常形式多囊蛋白的DNA突变引起的。多囊蛋白似乎在上皮细胞分化中具有正常作用，当出现缺陷时，这些细胞无法完全成熟。这些未完全分化的细胞异常增殖，并表达数量改变但其他方面正常的电解质转运蛋白，导致溶质和液体过度分泌到囊肿中。细胞的增殖及相关凋亡，以及液体分泌到由不断增大的肾小管节段形成的囊肿中，似乎受生长因子、激素和细胞因子调节，这些因子可改变个体间该疾病的临床表达程度。囊肿的形成与肾脏和其他器官细胞外基质的复杂变化有关，这些变化可能直接或间接与突变的多囊蛋白相关。这些致病因素的总和导致肾间质浸润，单核细胞、巨噬细胞和成纤维细胞最终导致纤维化和肾功能的进行性丧失。对囊肿发病机制的现代理解为开发可能减少或完全阻止该疾病进展的治疗方法提供了机会。
