Abnormal sodium pump distribution during renal tubulogenesis in congenital murine polycystic kidney disease.

Abstract

Congenital polycystic kidney disease is characterized by the formation of large fluid-filled cysts in kidney tubules. It has been postulated that increased epithelial cell proliferation and altered transtubular fluid transport are necessary for cyst formation. To address the latter problem, we have studied the plasma membrane distribution of the al and (31 subunits of Na+/K+-ATPase during progressive stages of proximal and collecting tubular cyst formation in the CPK mouse, a murine model of autosomal recessive polycystic kidney disease. In both control and cystic proximal tubules, Na+/K+-ATPase distribution was restricted to the basallateral membrane of cells. However, in newborn through day 5 kidney tissue, 16% of control vs. 47% of cystic outer cortical, 6% of control vs. 46% of cystic inner cortical, and 2% of control vs. 63% of cystic medullary collecting tubules demonstrated apical and lateral membrane distribution of Na+/K+-ATPase. In all nephrogenic zones, the percentage of control or cystic collecting tubules demonstrating apical membrane distribution of Na+/K+-ATPase decreased over time, but the percentage of cystic collecting tubules with apical membrane

Na Transport in Autosomal Recessive Polycystic Kidney Disease (ARPKD) Cyst Lining Epithelial Cells

“…It is well established that Na/K-ATPase normally polarizes to the basolateral membrane of fully differentiated mature collecting duct cells and is transiently expressed along the apical membrane of these nephron segments in fetal development (19) and murine models of ARPKD (8). However, it is unknown whether the apical pump, comprised of ␣1 and ␤2 subunits, is functional in these settings.…”

“…Within this segment, Na diffuses from the urinary space into principal cells through apical epithelial Na channels (ENaC) and is extruded at the basolateral membrane in exchange for uptake of K by the Na/K-ATPase (11). Murine models of ARPKD exhibit apical immunodetectable Na/KATPase in cystic collecting ducts (8), suggesting that cystlining epithelial cells in ARPKD may secrete Na, as in AD-PKD. Few studies have systematically attempted to define the transport characteristics of ARPKD cystic renal epithelia.…”

Epithelial-to-mesenchymal transition in cyst lining epithelial cells in an orthologous PCK rat model of autosomal-recessive polycystic kidney disease

“…Avner et al (3) reported that the apical membrane Na ϩ -K ϩ -ATPase ␣1-subunit persisted in cystic kidneys of the PCK mouse, suggesting that its expression might be a manifestation of the relatively undifferentiated phenotype of the epithelial cells lining CD cysts. Although there is a difference in the abnormal expression pattern of the Na ϩ -K ϩ -ATPase ␣1-subunit in cystic epithelium between the PCK rat and CPK mouse models, these findings may suggest diversity of the peripheral phenotype of epithelial cells from the common pathophysiology of PKD.…”

The Na+/K+ ATPase is required for septate junction function and epithelial tube-size control in theDrosophilatracheal system

“…Na + /K + ATPase in vertebrate epithelial tube-size disorders The Na + /K + ATPase has been implicated in vertebrate tubesize control by the abnormal subcellular localization of the Na + /K + ATPase in the inappropriately expanded tubules in individuals with PKD and in several animal models of cystic kidney diseases (Avner et al, 1992;Carone et al, 1995;Ogborn et al, 1995;Wilson et al, 2000;Wilson et al, 1991). However, it has not yet been determined whether this mislocalization contributes to the progression of cystic diseases or whether it is merely a secondary effect of other cellular defects.…”