Document Detail

Formation of cysts by principal-like MDCK cells depends on the synergy of cAMP- and ATP-mediated fluid secretion.
MedLine Citation:
PMID:  21206992     Owner:  NLM     Status:  MEDLINE    
It has been suggested that more than 70% of the renal cysts in patients with autosomal dominant polycystic kidney disease (ADPKD) arise from the collecting duct and that within this segment cysts originate almost exclusively from principal rather than intercalated cells. The mechanisms for this predisposition of principal cells have so far remained elusive. We, therefore, used Madin-Darby canine kidney (MDCK) subclones resembling principal cells and alpha-intercalated cells in a three-dimensional in vitro model to determine differences in cystogenesis and cyst growth, including the response to cyclic adenosine monophosphate (cAMP) elevation and the dependence on ATP signaling. We found that in vitro cysts developed only from principal-like but not from intercalated-like MDCK cell clones. This specificity could be verified in mixed MDCK cultures enriched for principal- or intercalated-like cells. In vitro cyst growth upon elevation of intracellular cAMP was mainly driven by fluid secretion, rather than increased cell proliferation. The cAMP-dependent fluid secretion was found to depend on extracellular adenosine-5'-triphosphate (ATP) and to act synergistically with purinergic signaling, as the use of the ATP scavenger apyrase, as well as the P2 receptor inhibitor suramin, reduced cAMP-driven fluid secretion, while increasing extracellular ATP potentiated cAMP-mediated cyst growth. In conclusion, we provide in vitro evidence for the ability of principal rather than intercalated cells to form cysts, based on a synergism of cAMP and ATP signaling in enhancing apical fluid secretion.
Bjoern Buchholz; Barbara Teschemacher; Gunnar Schley; Hermann Schillers; Kai-Uwe Eckardt
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-01-05
Journal Detail:
Title:  Journal of molecular medicine (Berlin, Germany)     Volume:  89     ISSN:  1432-1440     ISO Abbreviation:  J. Mol. Med.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-22     Completed Date:  2011-06-01     Revised Date:  2011-07-08    
Medline Journal Info:
Nlm Unique ID:  9504370     Medline TA:  J Mol Med (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  251-61     Citation Subset:  IM    
Department of Nephrology and Hypertension, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
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MeSH Terms
Adenosine Triphosphate / metabolism*
Blotting, Western
Cell Line
Cyclic AMP / metabolism*
Cysts / metabolism*
Reg. No./Substance:
56-65-5/Adenosine Triphosphate; 60-92-4/Cyclic AMP
Comment In:
J Mol Med (Berl). 2011 Mar;89(3):247-50   [PMID:  21301792 ]

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