Faculty Collaboration Database

Triiodothyronine-induced cyst formation in metanephric organ culture: the role of increased Na-K-adenosine triphosphatase activity. J Lab Clin Med 1987 Apr;109(4):441-53

Date

04/01/1987

Pubmed ID

3029256

Scopus ID

2-s2.0-45949117890 (requires institutional sign-in at Scopus site)   18 Citations

Abstract

Previous organ culture investigations into the pathogenesis of renal cyst formation have demonstrated that glucocorticoid-induced proximal tubular cyst formation is associated with increases in renal sodium-potassium adenosine triphosphatase (Na-K-ATPase) activity. To explore the relationship between cyst production and transport enzyme induction, we examined the effects of the potent inducer of Na-K-ATPase activity, L-3,5,3'-triiodothyronine (T3), on renal tubular morphologic and enzymatic development in murine metanephric organ culture. The addition of T3 (2 X 10(-8) mol/L) to completely characterized, serum-free growth medium produced striking proximal tubular cystic abnormalities. Frank cyst development was preceded by ultrastructural alterations consisting of basolateral intercellular spreading, which increased with progressive tubular dilation. Ultrastructural analysis demonstrated no abnormalities of tubular cyst wall basal laminae, and immunohistologic staining with affinity-purified antibodies to the basal lamina glycoproteins fibronectin, laminin, and entactin, revealed no differences between cystic and control tissue. With use of an enzyme-linked kinetic microassay, T3-induced cystic organ culture explants (CY) showed significant increases in Na-K-ATPase when compared with controls from 72 to 120 hours of organ culture incubation. The initial differences in CY Na-K-ATPase occurred contemporaneously with the earliest ultrastructural evidence of cyst formation, and subsequent increases paralleled progressive tubular cyst formation. Tubular cyst formation in CY could be largely prevented by daily incubation of explants with ouabain, 0.2 mmol/L (final concentration) for 120 minutes without deleterious effects on overall metanephric development. We conclude that T3 induces proximal tubular cyst formation in metanephric organ culture, and that T3-induced increases in Na-K-ATPase have a primary role in the pathogenesis of tubular cyst formation in this model system.

Author List

Avner ED, Sweeney WE Jr, Piesco NP, Ellis D

Author

Ellis D. Avner MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Basement Membrane
Enzyme Induction
Histocytochemistry
Immunoenzyme Techniques
Kidney
Kidney Diseases, Cystic
Kidney Tubules, Proximal
Mice
Organ Culture Techniques
Ouabain
Sodium-Potassium-Exchanging ATPase
Triiodothyronine