Horikoshi S, Kubota S, Martin G R, Yamada Y, Klotman P E
Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research, NIH, Bethesda, Maryland.
Kidney Int. 1991 Jan;39(1):57-62. doi: 10.1038/ki.1991.7.
The mechanisms responsible for renal cyst formation in congenital polycystic kidney disease remain unknown, although abnormalities of cellular metabolism, basement membrane components, and growth factors have been suggested. In the present study, we examined a potential role for epidermal growth factor (EGF) in cyst formation in a mouse model. We measured growth factor activity and concentration in renal cyst fluid, urine, and serum obtained from mice with congenital polycystic kidney disease (cpk). In affected mice, both growth factor activity of urine and the urinary EGF concentration were much lower than unaffected littermate controls even when corrected for creatinine concentration. Although the growth factor activity was much lower in affected mice, there were significant differences in the regional distribution of EGF in animals with cysts. Both growth factor activity and EGF concentration were greater in cyst fluid when compared to urine. Growth factor activity in cysts was completely inhibited by anti-EGF antibody using BALB/MK epithelial keratinocytes as targets. The expression of EGF mRNA in kidneys from affected mice was markedly decreased when compared to littermate controls. These results suggest that decreased EGF production and local differences in EGF concentration may contribute to cyst formation.
尽管有人提出细胞代谢、基底膜成分和生长因子存在异常，但先天性多囊肾病中肾囊肿形成的机制仍不清楚。在本研究中，我们在一个小鼠模型中研究了表皮生长因子（EGF）在囊肿形成中的潜在作用。我们测量了从患有先天性多囊肾病（cpk）的小鼠获得的肾囊肿液、尿液和血清中的生长因子活性和浓度。在患病小鼠中，即使校正了肌酐浓度，尿液的生长因子活性和尿表皮生长因子浓度也比未患病的同窝对照小鼠低得多。尽管患病小鼠的生长因子活性低得多，但囊肿动物中表皮生长因子的区域分布存在显著差异。与尿液相比，囊肿液中的生长因子活性和表皮生长因子浓度都更高。以BALB/MK上皮角质形成细胞为靶点，抗表皮生长因子抗体完全抑制了囊肿中的生长因子活性。与同窝对照相比，患病小鼠肾脏中表皮生长因子mRNA的表达明显降低。这些结果表明，表皮生长因子产生减少和表皮生长因子浓度的局部差异可能导致囊肿形成。
