Skip to main content
Log in

Juxtaglomerular cell tumor cell line producing active renin and its precursors

  • Original Articles
  • Published:
Virchows Archiv B

Summary

We have established tumor cell lines from a rare juxtaglomerular cell tumor (JGCT) of the kidney. The original tumor contained both neoplastic cells and a tubular component. The tumor cell line (JX-G) maintained a capacity for renin production after the 20th passage. Cells at the fourth and 16th passage strongly reacted immunocytochemically with an antihuman renin antibody. Western blot analysis at the 9th passage revealed a positive reaction for renin at Mr 45000 and Mr 62000 which corresponded to renin precursors. However, the total amount of active renin secreted into the culture medium was high in the primary culture, but undetectable after the 4th passage. These findings indicate that the JGCT cell lines produced both active and inactive renin and the primary cultured JGCT cells secreted active renin, but that the secretion of renin had diminished after several passages. Additional stimuli thus appear necessary for maturation of renin and its subsequent secretion. These findings and the presence of a tubular component in the original tumor suggest that some signal transduction system is maintained in JGCTs.

The physiological relationship of JGCT to the juxtaglomerular apparatus (JGA) and possible applications of the new cell lines are also discussed.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Barajas L, Bennett CM, Connor G, Lindstrom RR (1977) Structure of a juxtaglomerular cell tumor: the presence of neural component: A light and electron microscopic study. Lab Invest 37:357–368

    Article  PubMed  CAS  Google Scholar 

  • Barajas L (1979) Anatomy of the juxtaglomerular apparatus. Am J Physiol 237:333–343

    Google Scholar 

  • Bohle A, Christensen J, Kokot F, Osswald H, Schubert B, Kendziorra H, Pressler H, Marcovic-Lipkovski (1990) Acute renal failure in man: New aspects concerning pathogenesis. Am J Nephrol 10:374–388

    Article  PubMed  CAS  Google Scholar 

  • Briggs JP, Skøtt O, Schnermann J (1990) Cellular mechanisms within the juxtaglomerular apparatus. Am J Hypertens 3:76–80

    PubMed  CAS  Google Scholar 

  • Brown JJ, Fraser R, Lever AF, Morton JJ, Robertson JIS, Tree M, Bell PRF, Davidson JK, Ruthven IS (1973) Hypertension and secondary hyperaldosteronism associated with a reninsecreting renal juxtaglomerular-cell tumour. Lancet 2:1228–1231

    Article  PubMed  CAS  Google Scholar 

  • Conn JW, Cohen EL, Lucas CP, McDonald WJ, Mayor GH, Blough WM, Eveland WC, Bookstein JJ, Lapides J (1972) Primary reninism: hypertension, hyperreninemia, and secondary aldosteronism due to renin-producing juxtaglomerular cell tumors. Arch Int Med 130:682–696

    Article  CAS  Google Scholar 

  • Galen FX, Devaux C, Houot AM, Ménard J, Corvol P, Corvol MT, Gubler MC, Mounier F, Camilleri JP (1984a) Renin biosynthesis by human tumoral juxtaglomerular cells: Evidences for a renin precursor. J Clin Invest 73:1144–1155

    Article  PubMed  CAS  Google Scholar 

  • Galen FX, Devaux C, Atlas S, Guyenne T, Ménard J, Corvol P, Simon D, Cazaubon C, Richer P, Badouaille G, Richaud JP, Gros P, Pau B (1984b) New monoclonal antibodies directed against human renin: Powerful tools for the investigation of the renin system. J Clin Invest 74:723–735

    Article  PubMed  CAS  Google Scholar 

  • González E, Salomonsson M, Westerlund P, Persson AEG (1991) Optical studies on the action of furosemide on macula densa and cortical thick ascending limb cells. Intracellular calcium fluorescence measurements. Kidney Int [Suppl] 32:S55-S58

    Google Scholar 

  • Hirose M, Arakawa K, Kikuchi M, Kawasaki T, Omoto T, Kato H, Nagayama T (1974) Primary renism: With renal hamartomatous alteration. JAMA 230:1288–1292

    Article  PubMed  CAS  Google Scholar 

  • Hirose S, Kim S, Miyazaki H, Park Y, Murakami K (1985) In vitro biosynthesis of human renin and identification of plasma inactive renin as an activation intermediate. J Biol Chem 260:16400–16405

    PubMed  CAS  Google Scholar 

  • Ishizuka Y, Iizumi S, Akiyama F, Hori H, Poorman RA, Lobl TJ, Murakami K (1989) Characterization of monoclonal antibodies against human prorenin profragment and identification of active prorenins in plasma. J Biochem 106:430–435

    PubMed  CAS  Google Scholar 

  • Ito S, Carretero OA (1990) An in vitro approach to the study of macula densa-mediated glomerular hemodynamics. Kidney Int 38:1206–1210

    Article  PubMed  CAS  Google Scholar 

  • Ménard J, Bews J, Heusser C (1984) A multirange ELISA for the measurement of plasma renin in humans and primates. J Hypertens 2:S275-S278

    Google Scholar 

  • Minuth WW, Nobling R, Hackenthal E, Taugner R, Kriz W (1986) Long-term culture of renin containing tissue. Histochemistry 84:131–138

    Article  PubMed  CAS  Google Scholar 

  • More IAR, Jackson AM, Macsween RNM (1974) Renin-secreting tumor associated with hypertension Cancer 34:2093–2102

    Article  PubMed  CAS  Google Scholar 

  • Morgan T, Barrett G, Zhang Y, Alcorn D (1991) The role of the macula densa in renin synthesis. Clin Exp Pharmacol Physiol 18:123–126

    Article  PubMed  CAS  Google Scholar 

  • Morris BJ (1986) New possibilities for intracellular renin and inactive renin now that the structure of the human renin gene has been elucidated. Clin Sci 71:345–355

    PubMed  CAS  Google Scholar 

  • Osswald H, Muhlbauer B, Schenk F (1991) Adenosine mediates tubuloglomerular feedback response: an element of metabolic control of kidney function. Kidney Int [Suppl] 32:S128-S131

    CAS  Google Scholar 

  • Parmentier M, Inagami T, Pochet R A 45 000 molecular weight human renin precursor is synthesized in a cell-free translation system. Clin Sci 65:475–477

  • Pinet F, Corvol M, Dench F, Bourguignon J, Feunteun J, Menard J, Corvol P (1985) Isolation of renin-producing human cells by transfection with three simian virus 40 mutants. Proc Natl Acad Sci USA 82:8503–8507

    Article  PubMed  CAS  Google Scholar 

  • Pinet F, Mizrahi J, Laboulandine I, Menard J, Corvol P (1987) Regulation of prorenin secretion in cultured human transfected juxtaglomerular cells. J Clin Invest 80:724–731

    Article  PubMed  CAS  Google Scholar 

  • Remynse LC, Begun FP, Jacobs SC, Lawson RK (1989) Juxtaglomerular cell tumor with elevation of serum erythropoietin. J Urol 142:1560–1562

    PubMed  CAS  Google Scholar 

  • Rightsel WA, Okamura T, Inagami T, Pitcock JA, Takii Y, Brooks B, Brown P, Muirhead EE (1982) Juxtaglomerular cells grown as monolayer cell culture contain renin, angiotensin I-converting enzyme, and angiotensins I and II/III. Cire Res 50:822–829

    CAS  Google Scholar 

  • Schambelan M, Howes EL, Stockigt JR, Noakes CA, Biglieri FG (1973) Role of renin and aldosterone in hypertension due to a renin-secreting tumor. Am J Med 55:86–92

    Article  PubMed  CAS  Google Scholar 

  • Schnermann J, Weihprecht H, Lorenz JN, Briggs JP (1971) The afferent arteriole: The target for macula densa-generated signals. Kidney Int [Suppl] 32:S74-S77

    Google Scholar 

  • Tanaka T, Okumura A, Mori H (1993) Juxtaglomerular cell tumor. Arch Pathol Lab Med 117 (in press)

  • Thurau K (1964) Renal hemodynamics. Am J Med 36:698–719

    Article  PubMed  CAS  Google Scholar 

  • Thurau K, Schnermann J, Nagel W, Horster M, Wahl M (1967) Composition of tubular fluid in the macula densa segment as a factor regulating the function of the juxtaglomerular apparatus. Circ Res [Suppl] 2:79–89

    Google Scholar 

  • Towbin H, Stachelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76:4350–4353

    Article  PubMed  CAS  Google Scholar 

  • Weihprecht H, Lorenz JN, Schnermann J, Skøtt O, Briggs JP (1990) Effect of adenosine1-receptor blockade on renin release from rabbit isolated perfused juxtaglomerular apparatus. J Clin Invest 85:1622–1628

    Article  PubMed  CAS  Google Scholar 

  • Wright FS, Briggs JP (1979) Feedback control of glomerular blood flow, pressure, and filtration rate. Physiol Rev 59:958–1006

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Okumura, A., Tanaka, T. & Mori, H. Juxtaglomerular cell tumor cell line producing active renin and its precursors. Virchows Archiv B Cell Pathol 64, 303–307 (1993). https://doi.org/10.1007/BF02915127

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02915127

Key words

Navigation