This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barisoni, L. Articles by D'Agati, V. Search for Related Content PubMed PubMed Citation Articles by Barisoni, L. Articles by D'Agati, V.

American Journal of Pathology, Vol 147, 1728-1735, Copyright © 1995 by American Society for Investigative Pathology

REGULAR ARTICLES

Analysis of the role of membrane polarity in polycystic kidney disease of transgenic SBM mice

L Barisoni, M Trudel, N Chretien, L Ward, J van Adelsberg and V D'Agati
Department of Pathology, Columbia University, New York, New York 10032, USA.

Altered membrane polarity has been proposed as an important pathogenetic factor in the development of renal cysts in polycystic kidney disease. To determine whether this alteration in epithelial phenotype is a primary or secondary phenomenon, we examined the epithelial membrane polarity of SBM transgenic mice, in which epithelial proliferation mediated by the c-myc oncogene is an established primary event. Kidneys from 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 mice, Na,K-ATPase localization was apical in fetal kidneys but became translocated 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 58%), 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 cysts (mean 55%) in young transgenic mice but became less prevalent in adult 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 with cytoskeletal proteins ankyrin and fodrin. These heterogeneous patterns of Na,K-ATPase staining indicate that although altered cell polarity is frequent in early cystic epithelium of SBM mice, it is not a prerequisite to cystogenesis or progressive cyst enlargement. In conclusion, our results support the view that altered cystic membrane polarity is not a primary process, but represents the persistence of an immature epithelial phenotype characteristic of proliferative polycystic kidney disease epithelia.

This article has been cited by other articles:

				M. Levin THE EMBRYONIC ORIGINS OF LEFT-RIGHT ASYMMETRY Crit. Rev. Oral. Biol. Med., July 1, 2004; 15(4): 197 - 206. [Abstract] [Full Text] [PDF]

				M. Couillard, R. Guillaume, N. Tanji, V. D'Agati, and M. Trudel c-myc-induced Apoptosis in Polycystic Kidney Disease Is Independent of FasL/Fas Interaction Cancer Res., April 1, 2002; 62(8): 2210 - 2214. [Abstract] [Full Text] [PDF]

				L. P. SULLIVAN, D. P. WALLACE, and J. J. GRANTHAM Epithelial Transport in Polycystic Kidney Disease Physiol Rev, October 1, 1998; 78(4): 1165 - 1191. [Abstract] [Full Text] [PDF]

				M. Trudel, J. Lanoix, L. Barisoni, M.-J. Blouin, M. Desforges, C. L'Italien, and V. D'Agati C-MYC-induced Apoptosis in Polycystic Kidney Disease Is Bcl-2 and p53 Independent J. Exp. Med., December 1, 1997; 186(11): 1873 - 1884. [Abstract] [Full Text] [PDF]