RENAL EXPRESSION OF A TRANSFORMING GROWTH-FACTOR-ALPHA TRANSGENE ACCELERATES THE PROGRESSION OF INHERITED, SLOWLY PROGRESSIVE POLYCYSTIC KIDNEY-DISEASE IN THE MOUSE
Vh. Gattone et al., RENAL EXPRESSION OF A TRANSFORMING GROWTH-FACTOR-ALPHA TRANSGENE ACCELERATES THE PROGRESSION OF INHERITED, SLOWLY PROGRESSIVE POLYCYSTIC KIDNEY-DISEASE IN THE MOUSE, The Journal of laboratory and clinical medicine, 127(2), 1996, pp. 214-222
Citations number
38
Categorie Soggetti
Medical Laboratory Technology","Medicine, General & Internal
Polycystic kidney disease (PKD) is a prevalent inherited disease in hu
man beings. The pathogenesis of PKD is as yet unclear. The epidermal g
rowth factor family of proteins has been implicated in PKD based large
ly on in vitro data. To determine whether these growth factors contrib
ute to the progression of inherited PKD in vivo, we crossed mice with
a transgene for human transforming growth factor-alpha (TGF-alpha, a m
ember of the epidermal growth factor [EGF] family) and mice with the p
cy gene (which causes a slowly progressive form of PKD very similar to
human autosomal dominant PKD). Renal expression of the TGF-alpha tran
sgene In cystic mice (homozygous for the pcy gene) accelerated the dev
elopment of PKD as shown by an increased kidney weight as a percent of
body weight and an increased volume density of renal cysts at 8.5 wee
ks of age. However, renal expression of the TGF-alpha transgene did no
t appear to precociously initiate cyst development (at 6.5 weeks), nor
did it cause an increase in the final degree of renal enlargement (at
29 weeks). Thus TGF-alpha accelerated the enlargement of cysts once i
nitiated. At 8.5 weeks of age, renal expression of the TGF-alpha mRNA
correlated positively with the amount of renal enlargement. At all tim
e points studied, cystic kidneys exhibited increased expression of c-m
yc mRNA as compared with phenotypic normal kidneys, consistent with PK
D being a hyperplastic disease of renal tubules. However, the renal ex
pression of c-myc in 8.5 week cystic kidneys, with or without the tran
sgene, did not correlate with the degree of renal enlargement. The res
ults of this study suggest that EGF-like proteins may accelerate the p
rogression of inherited renal cystic disease. However, the final degre
e of cystic change is dictated by the primary disease process rather t
han by the continued presence of growth factor.