Fundamental Insights into Autosomal Dominant Polycystic Kidney Disease from Human-based Cell Models

Overview

Journal Pediatr Nephrol

Specialties Nephrology
Pediatrics

Date 2018 Sep 15

PMID 30215095

Citations 3

Authors

Caroline Weydert

Jean-Paul Decuypere

Humbert De Smedt

Peter Janssens

Rudi Vennekens

Djalila Mekahli

Affiliations

Soon will be listed here.

Abstract

Several animal- and human-derived models are used in autosomal dominant polycystic kidney disease (ADPKD) research to gain insight in the disease mechanism. However, a consistent correlation between animal and human ADPKD models is lacking. Therefore, established human-derived models are relevant to affirm research results and translate findings into a clinical set-up. In this review, we give an extensive overview of the existing human-based cell models. We discuss their source (urine, nephrectomy and stem cell), immortalisation procedures, genetic engineering, kidney segmental origin and characterisation with nephron segment markers. We summarise the most studied pathways and lessons learned from these different ADPKD models. Finally, we issue recommendations for the derivation of human-derived cell lines and for experimental set-ups with these cell lines.

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References

Tsiokas L, Arnould T, Zhu C, Kim E, Walz G, Sukhatme V . Specific association of the gene product of PKD2 with the TRPC1 channel. Proc Natl Acad Sci U S A. 1999; 96(7):3934-9. PMC: 22398. DOI: 10.1073/pnas.96.7.3934. View

Cordon-Cardo C, OBrien J, Boccia J, CASALS D, Bertino J, Melamed M . Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues. J Histochem Cytochem. 1990; 38(9):1277-87. DOI: 10.1177/38.9.1974900. View

Wilmer M, Saleem M, Masereeuw R, Ni L, van der Velden T, Russel F . Novel conditionally immortalized human proximal tubule cell line expressing functional influx and efflux transporters. Cell Tissue Res. 2009; 339(2):449-57. PMC: 2817082. DOI: 10.1007/s00441-009-0882-y. View

Knepper M, Brooks H . Regulation of the sodium transporters NHE3, NKCC2 and NCC in the kidney. Curr Opin Nephrol Hypertens. 2001; 10(5):655-9. DOI: 10.1097/00041552-200109000-00017. View

Pinto C, Reif G, Nivens E, White C, Wallace D . Calmodulin-sensitive adenylyl cyclases mediate AVP-dependent cAMP production and Cl- secretion by human autosomal dominant polycystic kidney cells. Am J Physiol Renal Physiol. 2012; 303(10):F1412-24. PMC: 3517630. DOI: 10.1152/ajprenal.00692.2011. View

Yamada H, Yamazaki S, Moriyama N, Hara C, Horita S, Enomoto Y . Localization of NBC-1 variants in human kidney and renal cell carcinoma. Biochem Biophys Res Commun. 2003; 310(4):1213-8. DOI: 10.1016/j.bbrc.2003.09.147. View

Wilmer M, Kluijtmans L, van der Velden T, Willems P, Scheffer P, Masereeuw R . Cysteamine restores glutathione redox status in cultured cystinotic proximal tubular epithelial cells. Biochim Biophys Acta. 2011; 1812(6):643-51. DOI: 10.1016/j.bbadis.2011.02.010. View

Ta M, Liuwantara D, Rangan G . Effects of pyrrolidine dithiocarbamate on proliferation and nuclear factor-κB activity in autosomal dominant polycystic kidney disease cells. BMC Nephrol. 2015; 16:212. PMC: 4678764. DOI: 10.1186/s12882-015-0193-3. View

Vandorpe D, Chernova M, Jiang L, Sellin L, Wilhelm S, Walz G . The cytoplasmic C-terminal fragment of polycystin-1 regulates a Ca2+-permeable cation channel. J Biol Chem. 2000; 276(6):4093-101. DOI: 10.1074/jbc.M006252200. View

10.

Chang M, Ong A . Targeting new cellular disease pathways in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2017; 33(8):1310-1316. DOI: 10.1093/ndt/gfx262. View

11.

Nouwen E, Dauwe S, Van der Biest I, De Broe M . Stage- and segment-specific expression of cell-adhesion molecules N-CAM, A-CAM, and L-CAM in the kidney. Kidney Int. 1993; 44(1):147-58. DOI: 10.1038/ki.1993.225. View

12.

Huang C, Ho M, Jia-Jung Lee , Hwang D, Ko H, Cheng Y . Generation of induced pluripotent stem cells derived from an autosomal dominant polycystic kidney disease patient with a p.Ser1457fs mutation in PKD1. Stem Cell Res. 2017; 24:139-143. DOI: 10.1016/j.scr.2017.09.004. View

13.

MAUNSBACH A, Marples D, Chin E, Ning G, BONDY C, Agre P . Aquaporin-1 water channel expression in human kidney. J Am Soc Nephrol. 1997; 8(1):1-14. DOI: 10.1681/ASN.V811. View

14.

Streets A, Magayr T, Huang L, Vergoz L, Rossetti S, Simms R . Parallel microarray profiling identifies ErbB4 as a determinant of cyst growth in ADPKD and a prognostic biomarker for disease progression. Am J Physiol Renal Physiol. 2017; 312(4):F577-F588. PMC: 5504395. DOI: 10.1152/ajprenal.00607.2016. View

15.

Venugopal J, Blanco G . Ouabain Enhances ADPKD Cell Apoptosis via the Intrinsic Pathway. Front Physiol. 2016; 7:107. PMC: 4805603. DOI: 10.3389/fphys.2016.00107. View

16.

Nauli S, Alenghat F, Luo Y, Williams E, Vassilev P, Li X . Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet. 2003; 33(2):129-37. DOI: 10.1038/ng1076. View

17.

Morel N, Vandenberg G, Ahrabi A, Caron N, Desjardins F, Balligand J . PKD1 haploinsufficiency is associated with altered vascular reactivity and abnormal calcium signaling in the mouse aorta. Pflugers Arch. 2008; 457(4):845-56. DOI: 10.1007/s00424-008-0561-y. View

18.

Putnam W, Swenson S, Reif G, Wallace D, Helmkamp Jr G, Grantham J . Identification of a forskolin-like molecule in human renal cysts. J Am Soc Nephrol. 2007; 18(3):934-43. DOI: 10.1681/ASN.2006111218. View

19.

Wang E, Hsieh-Li H, Chiou Y, Chien Y, Ho H, Chin H . Progressive renal distortion by multiple cysts in transgenic mice expressing artificial microRNAs against Pkd1. J Pathol. 2010; 222(3):238-48. DOI: 10.1002/path.2765. View

20.

Ben-Dov I, Tan Y, Morozov P, Wilson P, Rennert H, Blumenfeld J . Urine microRNA as potential biomarkers of autosomal dominant polycystic kidney disease progression: description of miRNA profiles at baseline. PLoS One. 2014; 9(1):e86856. PMC: 3906110. DOI: 10.1371/journal.pone.0086856. View