Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Aug;86(15):6007–6011. doi: 10.1073/pnas.86.15.6007

Renal epithelial cyst formation and enlargement in vitro: dependence on cAMP.

R Mangoo-Karim 1, M Uchic 1, C Lechene 1, J J Grantham 1
PMCID: PMC297761  PMID: 2474825

Abstract

Cysts, a common abnormality of kidneys, are collections of urine-like fluid enclosed by a continuous layer of epithelial cells. Renal cysts derive from nephrons and collecting ducts and progressively enlarge as a consequence of epithelial proliferation and transepithelial fluid secretion. The initiation of cyst formation and the factors that control cyst enlargement are unknown. We used an in vitro model of renal cysts to explore the role of the cAMP signal transduction system in the formation and expansion of cysts. MDCK cells, cultured in hydrated-collagen gel, produced polarized monolayered epithelial cysts when intracellular cAMP was increased by prostaglandin E1, arginine vasopressin, cholera toxin, forskolin, or 8-bromoadenosine 3',5'-cyclic monophosphate. All agonists were potentiated by 3-isobutyl-1-methylxanthine, a nucleotide phosphodiesterase inhibitor. The cell proliferation component of cyst enlargement was accelerated by cAMP agonists, as shown by the increased growth of MDCK cells in subconfluent monolayers. The fluid secretion component, reflected by the transepithelial movement of fluid across polarized monolayers of MDCK cells grown on permeable supports, was stimulated by cAMP agonists in the basolateral medium. Chloride levels were higher in the cyst fluid and the secreted fluid than in the bathing medium. We conclude that the development of MDCK cysts is dependent on cAMP. This signal transduction system may be an important modulator of epithelial cell proliferation and transepithelial fluid secretion in the kidney.

Full text

PDF
6007

Images in this article

6008Image
on p.6008

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Al-Bazzaz F., Yadava V. P., Westenfelder C. Modification of Na and Cl transport in canine tracheal mucosa by prostaglandins. Am J Physiol. 1981 Feb;240(2):F101–F105. doi: 10.1152/ajprenal.1981.240.2.F101. [DOI] [PubMed] [Google Scholar]
  2. Beyenbach K. W. Secretory NaCl and volume flow in renal tubules. Am J Physiol. 1986 May;250(5 Pt 2):R753–R763. doi: 10.1152/ajpregu.1986.250.5.R753. [DOI] [PubMed] [Google Scholar]
  3. Brown C. D., Simmons N. L. Catecholamine-stimulation of Cl- secretion in MDCK cell epithelium. Biochim Biophys Acta. 1981 Dec 7;649(2):427–435. doi: 10.1016/0005-2736(81)90432-6. [DOI] [PubMed] [Google Scholar]
  4. Carone F. A., Makino H., Kanwar Y. S. Basement membrane antigens in renal polycystic disease. Am J Pathol. 1988 Mar;130(3):466–471. [PMC free article] [PubMed] [Google Scholar]
  5. Cowley B. D., Jr, Smardo F. L., Jr, Grantham J. J., Calvet J. P. Elevated c-myc protooncogene expression in autosomal recessive polycystic kidney disease. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8394–8398. doi: 10.1073/pnas.84.23.8394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Els W. J., Helman S. I. Vasopressin, theophylline, PGE2, and indomethacin on active Na transport in frog skin: studies with microelectrodes. Am J Physiol. 1981 Sep;241(3):F279–F288. doi: 10.1152/ajprenal.1981.241.3.F279. [DOI] [PubMed] [Google Scholar]
  7. Grantham J. J., Geiser J. L., Evan A. P. Cyst formation and growth in autosomal dominant polycystic kidney disease. Kidney Int. 1987 May;31(5):1145–1152. doi: 10.1038/ki.1987.121. [DOI] [PubMed] [Google Scholar]
  8. Grantham J. J., Irwin R. L., Qualizza P. B., Tucker D. R., Whittier F. C. Fluid secretion in isolated proximal straight renal tubules. Effect of human uremic serum. J Clin Invest. 1973 Oct;52(10):2441–2450. doi: 10.1172/JCI107435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Grantham J. J., Uchic M., Cragoe E. J., Jr, Kornhaus J., Grantham J. A., Donoso V., Mangoo-Karim R., Evan A., McAteer J. Chemical modification of cell proliferation and fluid secretion in renal cysts. Kidney Int. 1989 Jun;35(6):1379–1389. doi: 10.1038/ki.1989.137. [DOI] [PubMed] [Google Scholar]
  10. Harris R. C., Seifter J. L., Lechene C. Coupling of Na-H exchange and Na-K pump activity in cultured rat proximal tubule cells. Am J Physiol. 1986 Nov;251(5 Pt 1):C815–C824. doi: 10.1152/ajpcell.1986.251.5.C815. [DOI] [PubMed] [Google Scholar]
  11. Heintze K., Stewart C. P., Frizzell R. A. Sodium-dependent chloride secretion across rabbit descending colon. Am J Physiol. 1983 Apr;244(4):G357–G365. doi: 10.1152/ajpgi.1983.244.4.G357. [DOI] [PubMed] [Google Scholar]
  12. Keeler R., Wong N. L. Evidence that prostaglandin E2 stimulates chloride secretion in cultured A6 renal epithelial cells. Am J Physiol. 1986 Mar;250(3 Pt 2):F511–F515. doi: 10.1152/ajprenal.1986.250.3.F511. [DOI] [PubMed] [Google Scholar]
  13. Lang M. A., Muller J., Preston A. S., Handler J. S. Complete response to vasopressin requires epithelial organization in A6 cells in culture. Am J Physiol. 1986 Jan;250(1 Pt 1):C138–C145. doi: 10.1152/ajpcell.1986.250.1.C138. [DOI] [PubMed] [Google Scholar]
  14. McAteer J. A., Evan A. P., Gardner K. D. Morphogenetic clonal growth of kidney epithelial cell line MDCK. Anat Rec. 1987 Mar;217(3):229–239. doi: 10.1002/ar.1092170303. [DOI] [PubMed] [Google Scholar]
  15. Rindler M. J., Chuman L. M., Shaffer L., Saier M. H., Jr Retention of differentiated properties in an established dog kidney epithelial cell line (MDCK). J Cell Biol. 1979 Jun;81(3):635–648. doi: 10.1083/jcb.81.3.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Taub M., Chuman L., Saier M. H., Jr, Sato G. Growth of Madin-Darby canine kidney epithelial cell (MDCK) line in hormone-supplemented, serum-free medium. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3338–3342. doi: 10.1073/pnas.76.7.3338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Welsh M. J., Widdicombe J. H., Nadel J. A. Fluid transport across the canine tracheal epithelium. J Appl Physiol Respir Environ Exerc Physiol. 1980 Nov;49(5):905–909. doi: 10.1152/jappl.1980.49.5.905. [DOI] [PubMed] [Google Scholar]
  18. Yanase M., Handler J. S. Activators of protein kinase C inhibit sodium transport in A6 epithelia. Am J Physiol. 1986 Mar;250(3 Pt 1):C517–C522. doi: 10.1152/ajpcell.1986.250.3.C517. [DOI] [PubMed] [Google Scholar]
  19. Zadunaisky J. A. Active transport of chloride in frog cornea. Am J Physiol. 1966 Aug;211(2):506–512. doi: 10.1152/ajplegacy.1966.211.2.506. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES