Skip to main content
SpringerLink
Log in

Transimmortalized proximal tubule and collecting duct cell lines derived from the kidneys of transgenic mice

  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

This review summarizes the strategy of cellular immortalization based on the principle of targeted oncogenesis in transgenic mice, used to establish models of transimmortalized renal proximal tubule cells, referred to as PKSV-PCT and PKSV-PR-cells, and collecting duct principal cells, referred to as mpkCCDcl4 cells. These cell lines have maintained for long-term passages the main biochemical and functional properties of the parental cells from which they were derived. Proximal tubule PKSV-PCT and PKSV-PR cells have been proved to be suitable cell systems for toxicological and pharmacological studies. They also permitted the establishment of a model of multidrug-resistant (MDR) renal epithelial tubule cells, PKSV-PRcol50, which have served for the study of both MDR-dependent extrusion of chemotherapeutic drugs and inappropriate accumulation of weak base anthracyclines in intracellular acidic organelles. The novel collecting duct cell line mpkCCDcl4, which has maintained the characteristics of tight epithelial cells, in particular Na+ absorption stimulated by aldosterone, has been extensively used for pharmacological studies related to the regulation of ion transport. These cells have permitted the identification of several aldosterone-induced proteins playing a key role in the regulation of Na+ absorption mediated by the epithelial Na+ channel ENaC. Recent studies have also provided evidence that these cell lines represent valuable cell systems for the study of host–pathogen interactions and the analysis of the role of renal tubule epithelial cells in the induction of inflammatory response caused by uropathogens that may lead to severe renal damage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CCD:

cortical collecting duct

DCT:

distal convoluted tubule

ENaC:

epithelial sodium channel

GILZ:

glucocorticoid-induced leucine zipper

IMCD:

inner medullary collecting duct

LPS:

lipopolysaccharide

mCAP1:

mouse channel activating protease 1MDR, multidrug-resistant

MR:

mineralocorticoid receptor

MRP:

multidrug resistance-associated protein

PRR:

pattern recognition receptor

TLR:

Toll-like receptor

UPEC:

uropathogenic E. coli

References

  • Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801.

    Article  PubMed  CAS  Google Scholar 

  • Atlan N, Chen Y, Schindler M, Simon SM. Defective acidification in human breast tumor cells and implications for chemotherapy. J Exp Med. 1998;187:1583–9.

    Article  Google Scholar 

  • Ayroldi E, Migliorati G, Bruscoli S, et al. Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappaB. Blood. 2001;98:743–53.

    Article  PubMed  CAS  Google Scholar 

  • Backhed F, Soderhall M, Ekman P, Normark S, Richter-Dahlfors A. Induction of innate immune responses by Escherichia coli and purified lipopolysaccharide correlate with organ- and cell-specific expression of Toll-like receptors within the human urinary tract. Cell Microbiol. 2001;3:153–8.

    Article  PubMed  CAS  Google Scholar 

  • Barton GM, Medzhitov R. Toll-like receptors and their ligands. Curr Top Microbiol Immunol. 2002;270:81–92.

    PubMed  CAS  Google Scholar 

  • Bens M, Bogdanova A, Cluzeaud F, et al. Transimmortalized intestinal cells (m-ICcl2) that maintain a crypt phenotype. Am J Physiol. 1996;270: C1666–74.

    PubMed  CAS  Google Scholar 

  • Bens M, Vallet V, Cluzeaud F, et al. Corticosteroid-dependent sodium transport in a novel immortalized mouse collecting duct principal cell line. J Am Soc Nephrol. 1999;10:923–34.

    PubMed  CAS  Google Scholar 

  • Berger FG, Watson G. Androgen-regulated gene expression. Annu Rev Physiol. 1989;51:51–65.

    Article  PubMed  CAS  Google Scholar 

  • Bixel I, Montano X, Agha M, et al. SV40 small t antigen enhances the transformation activity of limiting concentrations of SV40 large T antigen. Cell. 1987;48:321–30.

    Article  Google Scholar 

  • Briand P, Kahn A, Vandewalle A. Targeted oncogenesis: a powerful method to derive renal cell lines. Kidney Int. 1995;47:388–94.

    PubMed  CAS  Google Scholar 

  • Cartier N, Lacave R, Vallet V, et al. Establishment of proximal tubule cell lines by targeted oncogenesis in transgenic mice using the l-pyruvate kinase-SV40 (T) antigen hybrid gene. J Cell Sci. 1993;104:695–704.

    PubMed  CAS  Google Scholar 

  • Chassin C, Goujon JM, Darche S, et al. Renal collecting duct epithelial cells react to pyelonephritis-associated Escherichia coli by activating distinct TLR4-dependent and -independent inflammatory pathways. J Immunol. 2006;177:4773–84.

    PubMed  CAS  Google Scholar 

  • Chow JC, Young DW, Golenbock DT, Christ WJ, Gusovsky F. Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J Biol Chem. 1999;274:10689–92.

    Article  PubMed  CAS  Google Scholar 

  • Duc C, Farman N, Canessa CM, Bonvalet JP, Rossier BC. Cell-specific expression of epithelial sodium channel alpha, beta, and gamma subunits in aldosterone-responsive epithelia from the rat: localization by in situ hybridization and immunocytochemistry. J Cell Biol. 1994;127:1907–21.

    Article  PubMed  CAS  Google Scholar 

  • Duong Van Huyen JP, Bens M, Teulon J, Vandewalle A. Vasopressin-stimulated chloride transport in transimmortalized mouse cell lines derived from the distal convoluted tubule and cortical and inner medullary collecting ducts. Nephrol Dial Transplant. 2001;16:238–45.

    Article  Google Scholar 

  • Evers R, Zaman GJ, van Deemter L, et al. Basolateral localization and export activity of the human multidrug resistance-associated protein in polarized pig kidney cells. J Clin Invest. 1996;97:1211–8.

    PubMed  CAS  Google Scholar 

  • Fanning E, Knippers R. Structure and function of simian virus 40 large tumor antigen. Ann Rev Biochem. 1992;61:55–85.

    Article  PubMed  CAS  Google Scholar 

  • Farr RW. Leptospirosis. Clin Infect Dis. 1995;21:1–6.

    PubMed  CAS  Google Scholar 

  • Hung CC, Chang CT, Tian YC, et al. Leptospiral membrane proteins stimulate pro-inflammatory chemokines secretion by renal tubule epithelial cells through toll-like receptor 2 and p38 mitogen activated protein kinase. Nephrol Dial Transplant. 2006;21:898–910.

    Article  PubMed  CAS  Google Scholar 

  • Imamura K, Tanaka T. Pyruvate kinase isoenzymes from rats. Methods Enzymol. 1982;90:150–6.

    PubMed  CAS  Google Scholar 

  • Kamynina E, Debonneville C, Bens M, Vandewalle A, Staub O. A novel mouse Nedd4 protein suppresses the activity of the epithelial Na+ channel. FASEB J. 2001;15:204–14.

    Article  PubMed  CAS  Google Scholar 

  • Kamynina E, Staub O. Concerted action of ENaC, Nedd4-2, and Sgk1 in transepithelial Na+ transport. Am J Physiol Renal Physiol. 2002;283: F377–87.

    PubMed  CAS  Google Scholar 

  • Lacave R, Bens M, Cartier N, et al. Functional characteristics of proximal tubule cell lines derived from transgenic mice harboring l-pyruvate kinase-SV40 (T) antigen hybrid gene. J Cell Sci. 1993;104:705–12.

    PubMed  Google Scholar 

  • Lacave R, Ouar Z, Paulais M, et al. Lysosomotropic agents increase vinblastine efflux from mouse MDR proximal kidney cells exhibiting vectorial drug transport. J Cell Physiol. 1999;178:247–57.

    Article  PubMed  CAS  Google Scholar 

  • Letz B, Ackermann A, Canessa CM, Rossier BC, Korbmacher C. Amiloride-sensitive sodium channels in confluent M-1 mouse cortical collecting duct cells. J Membr Biol. 1995;148:127–41.

    PubMed  CAS  Google Scholar 

  • Letz B, Korbmacher C. cAMP stimulates CFTR-like Cl- channels and inhibits amiloride-sensitive Na+ channels in mouse CCD cells. Am J Physiol. 1997;272:C657–66.

    PubMed  CAS  Google Scholar 

  • Lien E, Means TK, Heine H, et al. Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide. J Clin Invest. 2000;105:497–504.

    Article  PubMed  CAS  Google Scholar 

  • Livingston D, Bradley P. The simian virus 40 large T antigen: a lot packed into a little. Mol Biol Med. 1987;4:63–80.

    PubMed  CAS  Google Scholar 

  • Miquerol L, Cluzeaud F, Porteu A, Alexandre Y, Vandewalle A, Kahn A. Tissue specificity of l-pyruvate kinase transgenes results from combinatorial effects of proximal promoter and distal activator regions. Gene Expression. 1996;5:315–30.

    PubMed  CAS  Google Scholar 

  • Munnich A, Marie J, Reach G, Vaulont S, Simon MP, Kahn A. In vivo hormonal control of L-type pyruvate kinase gene expression. Effects of glucagon, cyclic AMP, insulin, cortisone, and thyroid hormones on the dietary induction of mRNAs in the liver. J Biol Chem. 1984;259:10228–31.

    PubMed  CAS  Google Scholar 

  • Noguchi T, Yamada K, Inoue H, Matsuda T, Tanaka T. The L- and R-type isozymes of rat pyruvate kinase are produced from a single gene by use of different promoters. J Biol Chem. 1987;262:14366–71.

    PubMed  CAS  Google Scholar 

  • Ouar Z, Solé E, Bens M, Rafestin-Oblin ME, Meseguer A, Vandewalle A. Pleiotropic effects of dihydrotestosterone in immortalized mouse proximal cells. Kidney Int. 1998;53:59–66.

    Article  PubMed  CAS  Google Scholar 

  • Ouar Z, Lacave R, Bens M, Vandewalle A. Mechanisms of altered sequestration and efflux of chemotherapeutic drugs by multidrug resistant cells. Cell Biol Toxicol. 1999;15:91–100.

    Article  PubMed  CAS  Google Scholar 

  • Ouar Z, Bens M, Vignes C, et al. Vacuolar H+-ATPase inhibitors impair the preferential accumulation of daunomycin in lysosomes and reverse the resistance to anthracyclines in drug-resistant renal epithelial cells. Biochem J. 2003;370:185–93.

    Article  PubMed  CAS  Google Scholar 

  • Patole PS, Schubert S, Hildinger K, et al. Toll-like receptor-4: renal cells and bone marrow cells signal for neutrophil recruitment during pyelonephritis. Kidney Int. 2005;68:2582–7.

    Article  PubMed  CAS  Google Scholar 

  • Peng KC, Cluzeaud F, Bens M, et al. Tissue and cell distribution of the multidrug resistance-associated protein MRP in the mouse intestine and kidney. J Histochem Cytochem. 1999;47:747–68.

    Google Scholar 

  • Rafestin-Oblin ME, Fagart J, Souque A, Seguin C, Bens M, Vandewalle A. 11β-hydroxyprogesterone acts as a mineralocorticoid agonist in stimulating Na+ absorption in mammalian principal cortical collecting duct cell. Mol Pharmacol. 2002;62:1306–13.

    Article  PubMed  CAS  Google Scholar 

  • Riccaldi D, Robic D, Bens M, et al. Cultured proximal cells derived from transgenic mouse provide model to study drug toxicity. Kidney Int. 1995;48:722–30.

    PubMed  CAS  Google Scholar 

  • Robert-Nicoud M, Flahaut M, Elalouf JM, et al. Transcriptome of a mouse cortical collecting duct cell line: effects of aldosterone and vasopressin. Proc Natl Acad Sci USA. 2001;8:2712–6.

    Article  Google Scholar 

  • Rossier BC, Palmer LG. Mechanisms of aldosterone action on sodium and potassium transport. In: Seldin DW, Giebisch G, eds. The kidney: Physiology and Pathophysiology. New York: Raven Press; 1992:1373–409.

    Google Scholar 

  • Rubin H, Figge J, Bladon M, et al. Role of small t antigen in the acute transforming activity of SV40. Cell. 1982;30:469–80.

    Article  PubMed  CAS  Google Scholar 

  • Schindler M, Grabski S, Hoof E, Simon SM. Defective pH regulation of acidic compartments in human breast cancer cells (MCF-7) is normalized in adriamycin-resistant cells (MCF-7adr). Biochemistry. 1996;35:2811–7.

    Article  PubMed  CAS  Google Scholar 

  • Soundarajan R, Zhang TT, Wang J, Vandewalle A, Pearce D. A novel role for glucocorticoid leucine zipper protein in epithelial sodium channel-mediated sodium transport. J Biol Chem. 2005;48:39970–81.

    Article  CAS  Google Scholar 

  • Staub O, Verrey F. Impact of Nedd4 proteins and serum and glucocorticoid-induced kinases on epithelial Na+ transport in the distal nephron. J Am Soc Nephrol. 2005;16:3167–74.

    Article  PubMed  CAS  Google Scholar 

  • Stoos BA, Naray-Fejes-Toth A, Carretero OA, Ito S, Fejes-Toth G. Characterization of a mouse cortical collecting duct cell line. Kidney Int. 1991;39:1168–75.

    PubMed  CAS  Google Scholar 

  • Strober W, Murray PJ, Kitani A, Watanabe T. Signalling pathways and molecular interactions of NOD1 and NOD2. Nat Rev Immunol. 2006;6:9–20.

    Article  PubMed  CAS  Google Scholar 

  • Sweet BH, Hilleman MR. The vacuolating virus, S.V.40. Proc Soc Exp Med Biol Med. 1960;105:420–7.

    CAS  Google Scholar 

  • Takeuchi O, Hoshino K, Kawai T, et al. Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity. 1999;11:443–51.

    Article  PubMed  CAS  Google Scholar 

  • Tsuboi N, Yoshikai Y, Matsuo S, et al. Roles of toll-like receptors in C-C chemokine production by renal tubular epithelial cells. J Immunol. 2002;169:2026–33.

    PubMed  CAS  Google Scholar 

  • Vuagniaux G, Vallet V, Fowler Jeager N, et al. Activation of the amiloride-sensitive epithelial sodium channel by the mouse serine protease mCAP1 expressed in a mouse cortical collecting duct cell line. J Am Soc Nephrol. 2000;11:828–34.

    PubMed  CAS  Google Scholar 

  • Wolfs TG, Buurman WA, van Schadewijk A, et al. In vivo expression of Toll-like receptor 2 and 4 by renal epithelial cells: IFN-gamma and TNF-alpha mediated up-regulation during inflammation. J Immunol. 2002;168:1286–93.

    PubMed  CAS  Google Scholar 

  • Wu JH, Billings BJ, Balkovetz DF. Hepatocyte growth factor alters renal epithelial cell suceptibility to uropathogenic Escherichia coli. J Am Soc Nephrol. 2001;12:2543–53.

    PubMed  CAS  Google Scholar 

  • Yang CH, Wu MS, Pan M J, et al. The Leptospira outer membrane protein LipL32 induces tubulointerstitial nephritis-mediated gene expression in mouse proximal tubule cells. J Am Soc Nephrol. 2002;13:2037–45.

    Article  PubMed  CAS  Google Scholar 

  • Yang CW, Hung CC, Wu MS, et al. Toll-like receptor 2 mediates early inflammation by leptospiral outer membrane proteins in proximal tubule cells. Kidney Int. 2006;69:815–22.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon (CRB3), Paris, France

    C. Chassin, M. Bens & A. Vandewalle

  2. Université Paris 7 – Denis Diderot, Paris, France

    C. Chassin, M. Bens & A. Vandewalle

  3. INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon (CRB3), 16 rue Henri Huchard, BP 416, F-75018, Paris, France

    A. Vandewalle

Authors
  1. C. Chassin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Bens
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Vandewalle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Vandewalle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chassin, C., Bens, M. & Vandewalle, A. Transimmortalized proximal tubule and collecting duct cell lines derived from the kidneys of transgenic mice. Cell Biol Toxicol 23, 257–266 (2007). https://doi.org/10.1007/s10565-006-0169-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-006-0169-y

Keywords

Search

Navigation