Epidermal growth factor (EGF) expression in the congenital polycystic mouse kidney.
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.
Horikoshi
S
S
Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research, NIH, Bethesda, Maryland.
Kubota
S
S
Martin
G R
GR
Yamada
Y
Y
Klotman
P E
PE
D000818:Animals; D015152:Blotting, Northern; D002850:Chromatography, Gel; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry*; D051379:Mice; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D011863:Radioimmunoassay
D012333:RNA, Messenger; D004815:Epidermal Growth Factor