Year 2016 / Volume 108 / Number 2
Original
Overexpression of Aquaporin 1 on cysts of patients with polycystic liver disease

71-78

DOI: 10.17235/reed.2015.3960/2015

Dingyang Li, Xiaoju Shi, Lijing Zhao, Zuowen Liang, Shuli Xie, Guangyi Wang,

Abstract
Background and objective: Polycystic liver disease (PCLD) represents a group of genetic disorders that include autosomal dominant polycystic kidney disease (ADPKD) and isolated polycystic liver disease (iPCLD). There is currently no definitive treatment except for liver transplantation. The aim of this study was to assess the expression level of aquaporin 1 (AQP1) on the PCLD cysts with different sizes and provide the potential therapeutic target. Methods: We collected 3 normal bile ducts, and recruited 8 patients with simple liver cyst disease, 24 patients with ADPKD, and 17 patients with iPCLD. AQP1 expression in different types of cyst walls and in normal bile ducts was detected using real time quantitative PCR, western blot and immunofluorescence staining. We also compared AQP1 expression levels in cysts of different sizes. Besides, ionic concentrations, pH and osmolality of cyst fluid were analyzed. Results: The results showed that AQP1 expression in PCLD cysts was significantly higher than that in simple liver cysts and the normal bile ducts. In addition, a comparable increasing trend was found in cysts of smaller sizes to cysts of larger sizes. pH values, the sodium and chloride concentrations were higher in cyst fluid than that in the serum. Conclusions: AQP1 was overexpressed in cystic cholangiocytes. A tendency of increased AQP1 protein expression in correlation with the cyst size was also found. These observations offered a direction into the molecular mechanisms of cyst expansion and maybe provide new treatment strategies to reduce fluid secretion into liver cysts.
Share Button
New comment
Comments
No comments for this article
References
1. Abu-Wasel B, Walsh C, Keough V, Molinari M. Pathophysiology, epidemiology, classification and treatment options for polycystic liver diseases. World J Gastroenterol 2013;19:5775-86.
2. Temmerman F, Missiaen L, Bammens B, Laleman W, Cassiman D, Verslype C, et al. Systematic review: the pathophysiology and management of polycystic liver disease. Aliment Pharmacol Ther 2011;34:702-13.
3. Desmet VJ. Ludwig symposium on biliary disorders--part I. Pathogenesis of ductal plate abnormalities. Mayo Clin Proc 1998;73:80-9.
4. Fabris L, Cadamuro M, Fiorotto R, Roskams T, Spirli C, Melero S, et al. Effects of angiogenic factor overexpression by human and rodent cholangiocytes in polycystic liver diseases. Hepatology 2006;43:1001-12.
5. Qian Q, Du H, King BF, Kumar S, Dean PG, Cosio FG, et al. Sirolimus reduces polycystic liver volume in ADPKD patients. J Am Soc Nephrol 2008;19:631-8.
6. Huber VJ, Tsujita M, Nakada T. Aquaporins in drug discovery and pharmacotherapy. Mol Aspects Med 2012;33:691-703.
7. Splinter PL, Masyuk AI, LaRusso NF. Specific inhibition of AQP1 water channels in isolated rat intrahepatic bile duct units by small interfering RNAs. J Biol Chem 2003;278:6268-74.
8. Banales JM, Masyuk TV, Bogert PS, Huang BQ, Gradilone SA, Lee SO, et al. Hepatic cystogenesis is associated with abnormal expression and location of ion transporters and water channels in an animal model of autosomal recessive polycystic kidney disease. Am J Pathol 2008;173:1637-46.
9. Hayashi M, Yamaji Y, Monkawa T, Yoshida T, Tsuganezawa H, Sasamura H, et al. Expression and localization of the water channels in human autosomal dominant polycystic kidney disease. Nephron 1997;75:321-6.
10. Devuyst O. The expression of water channels AQP1 and AQP2 in a large series of ADPKD kidneys. Nephron 1998;78:116-7.
11. Devuyst O, Burrow CR, Smith BL, Agre P, Knepper MA, Wilson PD. Expression of aquaporins-1 and -2 during nephrogenesis and in autosomal dominant polycystic kidney disease. Am J Physiol 1996;271:169-83.
12. Pocsfalvi G, Raj DA, Fiume I, Vilasi A, Trepiccione F, Capasso G. Urinary extracellular vesicles as reservoirs of altered proteins during the pathogenesis of polycystic kidney disease. Proteomics Clin Appl 2015;9:552-67.
13. Drenth JP, Chrispijn M, Nagorney DM, Kamath PS, Torres VE. Medical and surgical treatment options for polycystic liver disease. Hepatology 2010;52:2223-30.
14. Hogan MC, Masyuk TV, Page LJ, Kubly VJ, Bergstralh EJ, Li X, et al. Randomized clinical trial of long-acting somatostatin for autosomal dominant polycystic kidney and liver disease. J Am Soc Nephrol 2010;21:1052-61.
15. Ravine D, Gibson RN, Walker RG, Sheffield LJ, Kincaid-Smith P, Danks DM. Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1. Lancet 1994;343:824-7.
16. Gigot JF, Jadoul P, Que F, Van Beers BE, Etienne J, Horsmans Y, et al. Adult polycystic liver disease: is fenestration the most adequate operation for long-term management? Ann Surg 1997;225:286-94.
17. Terryn S, Ho A, Beauwens R, Devuyst O. Fluid transport and cystogenesis in autosomal dominant polycystic kidney disease. Biochim Biophys Acta 2011;1812:1314-21.
18. Murray SL, Grubman SA, Perrone RD, Rojkind M, Moy E,Lee DW, et al. Matrix metalloproteinase activity in human intrahepatic biliary epithelial cell lines from patients with autosomal dominant polycystic kidney disease. Connect Tissue Res 1996;33:249-56.
19. Lee SO, Masyuk T, Splinter P, Banales JM, Masyuk A,Stroope A, et al. MicroRNA15a modulates expression of the cell-cycle regulator Cdc25A and affects hepatic cystogenesis in a rat model of polycystic kidney disease. J Clin Invest 2008;118:3714-24.
20. van Keimpema L, Nevens F, Vanslembrouck R, van Oijen MG, Hoffmann AL, Dekker HM, et al. Lanreotide reduces the volume of polycystic liver: a randomized, double-blind, placebo-controlled trial. Gastroenterology 2009;137:1661-8.
21. Qian Q. Isolated polycystic liver disease. Adv Chronic Kidney Dis 2010;17:181-9.
22. Everson GT, Emmett M, Brown WR, Redmond P, Thickman D. Functional similarities of hepatic cystic and biliary epithelium: studies of fluid constituents and in vivo secretion in response to secretin. Hepatology 1990;11:557-65.
23. Perrone RD, Grubman SA, Rogers LC, Lee DW, Moy E, Murray SL, et al. Continuous epithelial cell lines from ADPKD liver cysts exhibit characteristics of intrahepatic biliary epithelium. Am J Physiol 1995;269:335-45.
24. Hoevenaren IA, Wester R, Schrier RW, McFann K, Doctor RB, Drenth JP, et al. Polycystic liver: clinical characteristics of patients with isolated polycystic liver disease compared with patients with polycystic liver and autosomal dominant polycystic kidney disease. Liver Int 2008;28:264-70.
25. Masyuk T, Masyuk A, LaRusso N. Cholangiociliopathies: genetics, molecular mechanisms and potential therapies. Curr Opin Gastroenterol 2009;25:265-71.
26. Alvaro D, Gigliozzi A, Attili AF. Regulation and deregulation of cholangiocyte proliferation. J Hepatol 2000;33:333-40.
27. Waanders E, Van Krieken JH, Lameris AL, Drenth JP. Disrupted cell adhesion but not proliferation mediates cyst formation in polycystic liver disease. Mod Pathol 2008;21:1293-302.
28. Doctor RB, Johnson S, Brodsky KS, Amura CR, Gattone V, Fitz JG. Regulated ion transport in mouse liver cyst epithelial cells. Biochim Biophys Acta 2007;1772:345-54.
29.Banales JM, Prieto J, Medina JF. Cholangiocyte anion exchange and biliary bicarbonate excretion. World J Gastroenterol 2006;12:3496-511.
Related articles
Citation tools
Li D, Shi X, Zhao L, Liang Z, Xie S, Wang G, et all. Overexpression of Aquaporin 1 on cysts of patients with polycystic liver disease. 3960/2015


Download to a citation manager

Download the citation for this article by clicking on one of the following citation managers:

Metrics
This article has received 1608 visits.
This article has been downloaded 48 times.

Statistics from Dimensions


Statistics from Plum Analytics

Publication history

Received: 07/08/2015

Accepted: 09/11/2015

Online First: 30/11/2015

Published: 01/02/2016

Article revision time: 91 days

Article Online First time: 115 days

Article editing time: 178 days


Share
This article hasn't been rated yet.
Reader rating:
Valora este artículo:




Asociación Española de Ecografía Digestiva Sociedad Española de Endoscopia Digestiva Sociedad Española de Patología Digestiva
The Spanish Journal of Gastroenterology is the official organ of the Sociedad Española de Patología Digestiva, the Sociedad Española de Endoscopia Digestiva and the Asociación Española de Ecografía Digestiva
Cookie policy Privacy Policy Legal Notice © Copyright 2023 y Creative Commons. The Spanish Journal of Gastroenterology