ANALYSIS OF THE ROLE OF MEMBRANE POLARITY IN POLYCYSTIC KIDNEY-DISEASE OF TRANSGENIC SBM MICE

Citation
L. Barisoni et al., ANALYSIS OF THE ROLE OF MEMBRANE POLARITY IN POLYCYSTIC KIDNEY-DISEASE OF TRANSGENIC SBM MICE, The American journal of pathology, 147(6), 1995, pp. 1728-1735
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pathology
ISSN journal
0002-9440
Volume
147
Issue
6
Year of publication
1995
Pages
1728 - 1735
Database
ISI
SICI code
0002-9440(1995)147:6<1728:AOTROM>2.0.ZU;2-F
Abstract
Altered membrane polarity has been proposed as an important pathogenet ic factor in the development of renal cysts in polycystic kidney disea se. To determine whether this alteration in epithelial phenotype is a primary or secondary phenomenon, we examined the epithelial membrane p olarity of SBM transgenic mice, in which epithelial proliferation medi ated by the c-myc oncogene is an established primary event. Kidneys fr om 32 transgenic mice and 10 age-matched controls from fetal to adult age were immunostained with antibodies to Na,K-ATPase, fodrin, ankyrin , E-cadherin, and tubule segment-specific lectins. In normal control m ice, Na,K-ATPase localization was apical in fetal kidneys but became t ranslocated to the basolateral membrane at maturity. Early microcysts in fetal transgenic kidneys displayed similar (95 to 100%) apical Na,K -ATPase. In young and newborn transgenic mice (1 to 8 days of age), Na ,K-ATPase localization was extremely heterogeneous. Noncystic tubules demonstrated either apical (mean 23 to 28%), basolateral (mean 48 to 5 8%), mixed (mean 4 to 15%), or absent (mean 10 to 13%) staining for Na ,K-ATPase. Apical Na,K-ATPase was more frequently observed in early cy sts (mean 55%) in young transgenic mice but became less prevalent in a dult mice (mean 22%), where 30% of cysts had basolateral staining, 39% mixed patterns, and 9% absent staining. Macrocysts typically lost all Na,K-ATPase reactivity. At all ages, Na,K-ATPase colocalized well wit h cytoskeletal proteins ankyrin and fodrin. These heterogeneous patter ns of Na,K-ATPase staining indicate that although altered cell polarit y is frequent in early cystic epithelium of SBM mice, it is not a pre- requisite to cystogenesis or progressive cyst enlargement. In conclusi on, our results support the view that altered cystic membrane polarity is not a primary process, but represents the persistence of an immatu re epithelial phenotype characteristic of proliferative polycystic kid ney disease epithelia.