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The absence of prostaglandin E1 returned confluent cultures of highly proliferative murine polycystic kidney principal cells to a normal proliferation level

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Summary

Constitutively high proliferation, loss of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA)-regulated proliferation, and half-normal cAMP levels were observed previously in principal cells from the C57BL/6J-Cycl cpk (cpk) model of autosomal recessive polycystic kidneys disease (PKD) cultured in defined medium supplemented with prostaglandin E1 (PGE1). Because PGE1 can up- or down-regulate renal cAMP production depending upon its receptor coupling; cAMP exerted both PKA-dependent and PKA-independent effects on cell proliferation; proliferation is considered to be a component of cystogenesis; and PGE1 resulted in loss of tubular structures and formation of cystic structures in gel culture of Madin Darby Canine Kidney cells; the effect of removing PGE1 on murine principal cell proliferation was examined. Proliferation was measured in filter-grown cultures of cystic (cpk) and noncystic (C57) principal cells from cpk and C57BL/6J mice, respectively. Lack of PGE1 had no effect on subconfluent C57 and cpk cultures or confluent C57 cultures but had a dramatic effect on confluent cpk cultures. Without PGE1, cpk proliferation was comparble with the low C57 level. In PGE1-deficient medium, differences were observed between confluence conditions and cell types for responses to a cAMP analog and a PKA activity inhibitor that suggested altered regulation of both PKA-dependent and PKA-independent cell proliferation. Cyclic adenosine monophosphate-dependent differences reported here, and previously, support the idea that the combination of mutant PKD gene product, altered PGE1 responsiveness, and altered PKA targeting contributes to activation of a cystogenic signaling pathway that regulates principal cell proliferation and is involved in pathogenesis.

Key words

epithelia protein kinase A cyclic AMP cAMP PKA 

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Copyright information

© Society for In Vitro Biology 2003

Authors and Affiliations

  • Stephanie A. Orellana
    • 1
    • 2
    • 3
  • Andrea M. Quiñones
    • 1
  1. 1.Department of PediatricsCase Western Reserve University School of MedicineCleveland
  2. 2.Department of Physiology and BiophysicsCase Western Researve University School of MedicineCleveland
  3. 3.The Rainbow Center for Childhood PKDRainbow Babies and Children's Hospital University Hospitals of Cleveland, Research InstituteCleveland

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