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.
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Orellana, S.A., Quiñones, A.M. The absence of prostaglandin E1 returned confluent cultures of highly proliferative murine polycystic kidney principal cells to a normal proliferation level. In Vitro Cell.Dev.Biol.-Animal 39, 199–203 (2003). https://doi.org/10.1290/1543-706X(2003)039<0199:TAOPER>2.0.CO;2
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DOI: https://doi.org/10.1290/1543-706X(2003)039<0199:TAOPER>2.0.CO;2