| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
PHYSIOLOGICAL REVIEWS Vol. 78 No. 4 October 1998,
pp. 1165-1191
Copyright ©1998 The American Physiological Society
Departments of Molecular and Integrative Physiology, Medicine, and Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas
Sullivan, Lawrence P., Darren P. Wallace, and Jared J. Grantham. Epithelial Transport in Polycystic Kidney Disease. Physiol. Rev. 78: 1165-1191, 1998. 
In autosomal dominant polycystic kidney disease (ADPKD), the genetic defect results in the slow growth of a multitude of epithelial cysts within the renal parenchyma. Cysts originate within the glomeruli and all tubular structures, and their growth is the result of proliferation of incompletely differentiated epithelial cells and the accumulation of fluid within the cysts. The majority of cysts disconnect from tubular structures as they grow but still accumulate fluid within the lumen. The fluid accumulation is the result of secretion of fluid driven by active transepithelial Cl
secretion. Proliferation of the cells and fluid secretion are activated by agonists of the cAMP signaling pathway. The transport mechanisms involved include the cystic fibrosis transmembrane conductance regulator (CFTR) present in the apical membrane of the cystic cells and a bumetanide-sensitive transporter located in the basolateral membrane. A lipid factor, called cyst activating factor, has been found in the cystic fluid. Cyst activating factor stimulates cAMP production, proliferation, and fluid secretion by cultured renal epithelial cells and also is a chemotactic agent. Cysts also appear in the intrahepatic biliary tree in ADPKD. Normal ductal cells secrete Cl and HCO3. The cystic ductal cell also secretes Cl, but HCO3 secretion is diminished, probably as the result of a lower population of Cl/HCO3 exchangers in the apical membrane as compared with the normal cells. Some segments of the normal renal tubule are also capable of utilizing CFTR to secrete Cl, particularly the inner medullary collecting duct. The ability of Madin-Darby canine kidney cells and normal human kidney cortex cells to form cysts in culture and to secrete fluid and the functional similarities between these incompletely differentiated, proliferative cells and developing cells in the intestinal crypt and in the fetal lung have led us to suggest that Cl and fluid secretion may be a common property of at least some renal epithelial cells in an intermediate stage of development. The genetic defect in ADPKD may not directly affect membrane transport mechanisms but rather may arrest the development of certain renal epithelial cells in an incompletely differentiated, proliferative stage.
This article has been cited by other articles:
|
|
 |
|
  B. Yang, N. D. Sonawane, D. Zhao, S. Somlo, and A. S. Verkman Small-Molecule CFTR Inhibitors Slow Cyst Growth in Polycystic Kidney Disease J. Am. Soc. Nephrol., July 1, 2008; 19(7): 1300 - 1310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Elberg, D. Elberg, T. V. Lewis, S. Guruswamy, L. Chen, C. J. Logan, M. D. Chan, and M. A. Turman EP2 receptor mediates PGE2-induced cystogenesis of human renal epithelial cells Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1622 - F1632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. C. Putnam, S. M. Swenson, G. A. Reif, D. P. Wallace, G. M. Helmkamp Jr., and J. J. Grantham Identification of a Forskolin-Like Molecule in Human Renal Cysts J. Am. Soc. Nephrol., March 1, 2007; 18(3): 934 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-N. T. Nguyen, D. P. Wallace, and G. Blanco Ouabain Binds with High Affinity to the Na,K-ATPase in Human Polycystic Kidney Cells and Induces Extracellular Signal-Regulated Kinase Activation and Cell Proliferation J. Am. Soc. Nephrol., January 1, 2007; 18(1): 46 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Olteanu, M. B. Hovater, and E. M. Schwiebert Intraluminal autocrine purinergic signaling within cysts: implications for the progression of diseases that involve encapsulated cyst formation Am J Physiol Renal Physiol, January 1, 2007; 292(1): F11 - F14. [Full Text] [PDF]
|
|
|
|
|
|
B. S. Magenheimer, P. L. St. John, K. S. Isom, D. R. Abrahamson, R. C. De Lisle, D. P. Wallace, R. L. Maser, J. J. Grantham, and J. P. Calvet Early Embryonic Renal Tubules of Wild-Type and Polycystic Kidney Disease Kidneys Respond to cAMP Stimulation with Cystic Fibrosis Transmembrane Conductance Regulator/Na+,K+,2Cl- Co-Transporter-Dependent Cystic Dilation J. Am. Soc. Nephrol., December 1, 2006; 17(12): 3424 - 3437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cooper, J. R. Latendresse, D. R. Doerge, N. C. Twaddle, X. Fu, and K. B. Delclos Dietary Modulation of p-Nonylphenol-Induced Polycystic Kidneys in Male Sprague-Dawley Rats Toxicol. Sci., June 1, 2006; 91(2): 631 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Banizs, M. M. Pike, C. L. Millican, W. B. Ferguson, P. Komlosi, J. Sheetz, P. D. Bell, E. M. Schwiebert, and B. K. Yoder Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus Development, December 1, 2005; 132(23): 5329 - 5339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zatti, V. Chauvet, V. Rajendran, T. Kimura, P. Pagel, and M. J. Caplan The C-Terminal Tail of the Polycystin-1 Protein Interacts with the Na,K-ATPase {alpha}-Subunit Mol. Biol. Cell, November 1, 2005; 16(11): 5087 - 5093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Montalbetti, Q. Li, G. A Timpanaro, S. Gonzalez-Perrett, X.-Q. Dai, X.-Z. Chen, and H. F Cantiello Cytoskeletal regulation of calcium-permeable cation channels in the human syncytiotrophoblast: role of gelsolin J. Physiol., July 15, 2005; 566(2): 309 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Markadieu, R. Crutzen, D. Blero, C. Erneux, and R. Beauwens Hydrogen peroxide and epidermal growth factor activate phosphatidylinositol 3-kinase and increase sodium transport in A6 cell monolayers Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1201 - F1212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. E. Veizis and C. U. Cotton Abnormal EGF-dependent regulation of sodium absorption in ARPKD collecting duct cells Am J Physiol Renal Physiol, March 1, 2005; 288(3): F474 - F482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Tong and J. D. Stockand Receptor tyrosine kinases mediate epithelial Na+ channel inhibition by epidermal growth factor Am J Physiol Renal Physiol, January 1, 2005; 288(1): F150 - F161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Puri, B. S. Magenheimer, R. L. Maser, E. M. Ryan, C. A. Zien, D. D. Walker, D. P. Wallace, S. J. Hempson, and J. P. Calvet Polycystin-1 Activates the Calcineurin/NFAT (Nuclear Factor of Activated T-cells) Signaling Pathway J. Biol. Chem., December 31, 2004; 279(53): 55455 - 55464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Loghman-Adham, C. E. Soto, T. Inagami, and L. Cassis The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease Am J Physiol Renal Physiol, October 1, 2004; 287(4): F775 - F788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yamaguchi, D. P. Wallace, B. S. Magenheimer, S. J. Hempson, J. J. Grantham, and J. P. Calvet Calcium Restriction Allows cAMP Activation of the B-Raf/ERK Pathway, Switching Cells to a cAMP-dependent Growth-stimulated Phenotype J. Biol. Chem., September 24, 2004; 279(39): 40419 - 40430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. N. Sheppard CFTR Channel Pharmacology: Novel Pore Blockers Identified by High-throughput Screening J. Gen. Physiol., July 26, 2004; 124(2): 109 - 113. [Full Text] [PDF]
|
|
|
|
|
|
H. F. Cantiello Regulation of calcium signaling by polycystin-2 Am J Physiol Renal Physiol, June 1, 2004; 286(6): F1012 - F1029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Venglarik, Z. Gao, and X. Lu Evolutionary Conservation of Drosophila Polycystin-2 as a Calcium-Activated Cation Channel J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1168 - 1177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Beyenbach Kidneys sans glomeruli Am J Physiol Renal Physiol, May 1, 2004; 286(5): F811 - F827. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wang, Y. Luo, P. D. Wilson, G. B. Witman, and J. Zhou The Autosomal Recessive Polycystic Kidney Disease Protein Is Localized to Primary Cilia, with Concentration in the Basal Body Area J. Am. Soc. Nephrol., March 1, 2004; 15(3): 592 - 602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. I. Veizis, C. R. Carlin, and C. U. Cotton Decreased amiloride-sensitive Na+ absorption in collecting duct principal cells isolated from BPK ARPKD mice Am J Physiol Renal Physiol, February 1, 2004; 286(2): F244 - F254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Wildman, K. M. Hooper, C. M. Turner, J. S. K. Sham, E. G. Lakatta, B. F. King, R. J. Unwin, and M. Sutters The isolated polycystin-1 cytoplasmic COOH terminus prolongs ATP-stimulated Cl- conductance through increased Ca2+ entry Am J Physiol Renal Physiol, December 1, 2003; 285(6): F1168 - F1178. [Abstract] [Full Text]
|
|
|
|
 |
|
 O. Devuyst, A. Persu, and M.-T. Vo-Cong Autosomal dominant polycystic kidney disease: modifier genes and endothelial dysfunction Nephrol. Dial. Transplant., November 1, 2003; 18(11): 2211 - 2215. [Full Text] [PDF]
|
|
|
|
|
|
D. Zheng, M. Wolfe, B. D. Cowley Jr., D. P. Wallace, T. Yamaguchi, and J. J. Grantham Urinary Excretion of Monocyte Chemoattractant Protein-1 in Autosomal Dominant Polycystic Kidney Disease J. Am. Soc. Nephrol., October 1, 2003; 14(10): 2588 - 2595. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Rajasekaran and S. A. Rajasekaran Role of Na-K-ATPase in the assembly of tight junctions Am J Physiol Renal Physiol, September 1, 2003; 285(3): F388 - F396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Hocher, P. Kalk, T. Slowinski, M. Godes, A. Mach, S. Herzfeld, D. Wiesner, P. C. Arck, H.-H. Neumayer, and B. Nafz ETA Receptor Blockade Induces Tubular Cell Proliferation and Cyst Growth in Rats with Polycystic Kidney Disease J. Am. Soc. Nephrol., February 1, 2003; 14(2): 367 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Morgan, L. Eley, J. Sayer, T. Strachan, L. M. Yates, A. S. Craighead, and J. A. Goodship Expression analyses and interaction with the anaphase promoting complex protein Apc2 suggest a role for inversin in primary cilia and involvement in the cell cycle Hum. Mol. Genet., December 15, 2002; 11(26): 3345 - 3350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Devuyst and W. B. Guggino Chloride channels in the kidney: lessons learned from knockout animals Am J Physiol Renal Physiol, December 1, 2002; 283(6): F1176 - F1191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.D. Gong, P. Linsdell, K.H. Cheung, G.P.H. Leung, and P.Y.D. Wong Indazole Inhibition of Cystic Fibrosis Transmembrane Conductance Regulator Cl- Channels in Rat Epididymal Epithelial Cells Biol Reprod, December 1, 2002; 67(6): 1888 - 1896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Wallace, M. Christensen, G. Reif, F. Belibi, B. Thrasher, D. Herrell, and J. J. Grantham Electrolyte and fluid secretion by cultured human inner medullary collecting duct cells Am J Physiol Renal Physiol, December 1, 2002; 283(6): F1337 - F1350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. P. Sullivan, D. P. Wallace, T. Gover, P. A. Welling, T. Yamaguchi, R. Maser, J. W. Eppler, and J. J. Grantham Sulfonylurea-Sensitive K+ Transport is Involved in Cl- Secretion and Cyst Growth by Cultured ADPKD Cells J. Am. Soc. Nephrol., November 1, 2002; 13(11): 2619 - 2627. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. Belibi, D. P. Wallace, T. Yamaguchi, M. Christensen, G. Reif, and J. J. Grantham The Effect of Caffeine on Renal Epithelial Cells from Patients with Autosomal Dominant Polycystic Kidney Disease J. Am. Soc. Nephrol., November 1, 2002; 13(11): 2723 - 2729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Watts III and D. W. Good ERK mediates inhibition of Na+/H+ exchange and HCO3- absorption by nerve growth factor in MTAL Am J Physiol Renal Physiol, June 1, 2002; 282(6): F1056 - F1063. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Cai and D. N. Sheppard Phloxine B Interacts with the Cystic Fibrosis Transmembrane Conductance Regulator at Multiple Sites to Modulate Channel Activity J. Biol. Chem., May 24, 2002; 277(22): 19546 - 19553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Grantham and D. P. Wallace Return of the secretory kidney Am J Physiol Renal Physiol, January 1, 2002; 282(1): F1 - F9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Wallace, L. A. Rome, L. P. Sullivan, and J. J. Grantham cAMP-dependent fluid secretion in rat inner medullary collecting ducts Am J Physiol Renal Physiol, June 1, 2001; 280(6): F1019 - F1029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.P.H. Leung, X.D. Gong, K.H. Cheung, S.B. Cheng-Chew, and P.Y.D. Wong Expression of Cystic Fibrosis Transmembrane Conductance Regulator in Rat Efferent Duct Epithelium Biol Reprod, May 1, 2001; 64(5): 1509 - 1515. [Abstract] [Full Text]
|
|
|
|
|
|
K. NAKANISHI, W. E. SWEENEY JR., K. MACRAE DELL, C. U. COTTON, and E. D. AVNER Role of CFTR in Autosomal Recessive Polycystic Kidney Disease J. Am. Soc. Nephrol., April 1, 2001; 12(4): 719 - 725. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Grantham and J. P. Calvet Polycystic kidney disease: In danger of being X-rated? PNAS, January 30, 2001; 98(3): 790 - 792. [Full Text] [PDF]
|
|
|
|
|
|
S. González-Perrett, K. Kim, C. Ibarra, A. E. Damiano, E. Zotta, M. Batelli, P. C. Harris, I. L. Reisin, M. A. Arnaout, and H. F. Cantiello Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel PNAS, December 22, 2000; (2000) 21456598. [Abstract] [Full Text]
|
|
|
|
|
|
A. PERSU, O. DEVUYST, N. LANNOY, R. MATERNE, G. BROSNAHAN, P. A. GABOW, Y. PIRSON, and C. VERELLEN-DUMOULIN CF Gene and Cystic Fibrosis Transmembrane Conductance Regulator Expression in Autosomal Dominant Polycystic Kidney Disease J. Am. Soc. Nephrol., December 1, 2000; 11(12): 2285 - 2296. [Abstract] [Full Text]
|
|
|
|
|
|
S. H. Low, M. Miura, P. A. Roche, A. C. Valdez, K. E. Mostov, and T. Weimbs Intracellular Redirection of Plasma Membrane Trafficking after Loss of Epithelial Cell Polarity Mol. Biol. Cell, September 1, 2000; 11(9): 3045 - 3060. [Abstract] [Full Text]
|
|
|
|
|
|
S. M. Huber, G. S. Braun, S. Segerer, R. W. Veh, and M. F. Horster Metanephrogenic mesenchyme-to-epithelium transition induces profound expression changes of ion channels Am J Physiol Renal Physiol, July 1, 2000; 279(1): F65 - F76. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. HANAOKA and W. B. GUGGINO cAMP Regulates Cell Proliferation and Cyst Formation in Autosomal Polycystic Kidney Disease Cells J. Am. Soc. Nephrol., July 1, 2000; 11(7): 1179 - 1187. [Abstract] [Full Text]
|
|
|
|
|
|
A. Persu and O. Devuyst Transepithelial chloride secretion and cystogenesis in autosomal dominant polycystic kidney disease Nephrol. Dial. Transplant., June 1, 2000; 15(6): 747 - 750. [Full Text] [PDF]
|
|
|
|
 |
|
 N. McCarty Permeation through the CFTR chloride channel J. Exp. Biol., January 7, 2000; 203(13): 1947 - 1962. [Abstract] [PDF]
|
|
|
|
|
|
P. Upadhya, E. H. Birkenmeier, C. S. Birkenmeier, and J. E. Barker Mutations in a NIMA-related kinase gene, Nek1, cause pleiotropic effects including a progressive polycystic kidney disease in mice PNAS, January 4, 2000; 97(1): 217 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. VOGLER, S. HOMAN, A. PUNG, C. THORPE, J. BARKER, E. H. BIRKENMEIER, and P. UPADHYA Clinical and Pathologic Findings in Two New Allelic Murine Models of Polycystic Kidney Disease J. Am. Soc. Nephrol., December 1, 1999; 10(12): 2534 - 2539. [Abstract] [Full Text]
|
|
|
|
|
|
S. A. Orellana and C. Marfella-Scivittaro Distinctive Cyclic AMP-dependent Protein Kinase Subunit Localization Is Associated with Cyst Formation and Loss of Tubulogenic Capacity in Madin-Darby Canine Kidney Cell Clones J. Biol. Chem., July 7, 2000; 275(28): 21233 - 21240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Vandorpe, M. N. Chernova, L. Jiang, L. K. Sellin, S. Wilhelm, A. K. Stuart-Tilley, G. Walz, and S. L. Alper The Cytoplasmic C-terminal Fragment of Polycystin-1 Regulates a Ca2+-permeable Cation Channel J. Biol. Chem., February 2, 2001; 276(6): 4093 - 4101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gonzalez-Perrett, K. Kim, C. Ibarra, A. E. Damiano, E. Zotta, M. Batelli, P. C. Harris, I. L. Reisin, M. A. Arnaout, and H. F. Cantiello From the Cover: Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel PNAS, January 30, 2001; 98(3): 1182 - 1187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Schwiebert, D. P. Wallace, G. M. Braunstein, S. R. King, J. Peti-Peterdi, K. Hanaoka, W. B. Guggino, L. M. Guay-Woodford, P. D. Bell, L. P. Sullivan, et al. Autocrine extracellular purinergic signaling in epithelial cells derived from polycystic kidneys Am J Physiol Renal Physiol, April 1, 2002; 282(4): F763 - F775. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
