Skip to main content
SpringerLink
Log in

Altered renal morphology in transgenic mice with cholecystokinin overexpression

  • Original Paper
  • Published:
Transgenic Research Aims and scope Submit manuscript

Abstract

Although cholecystokinin is a regulatory peptide with a predominant role in the brain and the gastrointestinal tract, there is an increasing evidence for its role in the kidney. The aim of this study was to reveal morphological changes in the structure of kidney of mice with cholecystokinin overexpression by means of light, transmission and scanning electron microscope, and atomic force microscopy. Using immunohistochemistry the expression of important basement membrane proteins collagen IV, laminin and fibronectin, as well the distribution of cholecystokinin-8 in the renal structures was evaluated. The altered morphology of kidneys of mice with cholecystokinin overexpression was seen by all microscopic techniques used. The renal corpuscles were relatively small with narrow capsular lumen. The basement membranes of renal tubules were thickened and the epithelial cells were damaged, which was more pronounced for distal tubules. Characteristic feature was the increased number of vesicles seen throughout the epithelial cells of proximal and especially in distal tubules reflecting to the enhanced cellular degeneration. The relative expression of laminin but not collagen IV in the glomerular basement membrane was higher than in the tubular basement membranes. The content of fibronectin, in opposite, was higher in tubular membranes. Cholecystokinin-8 was clearly expressed in the glomeruli, in Bowman’s capsule, in proximal and distal tubules, and in collecting ducts. Ultrastructural studies showed irregularly thickened glomerular basement membranes to which elongated cytopodia of differently shaped podocytes were attached. As foot processes were often fused the number of filtration pores was decreased. In conclusion, cholecystokinin plays important role in renal structural formation and in functioning as different aspects of urine production in mice with cholecystokinin overexpression are affected-the uneven glomerular basement membrane thickening, structural changes in podocytes and in filtration slits affect glomerular filtration, while damaged tubular epithelial cells and changed composition of thickened tubular basement membranes affect reabsorption.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Aunapuu M (2004) Morphological changes in the Wistar rat kidney after renal mass ablation, low-dose irradiation and treatment. Dissertation, Estonian Agricultural University

  • Beinfeld MC (1983) Cholecystokinin in the central nervous system: a minireview. Neuropeptides 20:547–565

    Google Scholar 

  • Brees DK, Ogle RC, Williams JC (1995) Laminin and fibronectin content of mouse glomerular and tubular basement membrane. Ren Physiol Biochem 18:1–11

    PubMed  CAS  Google Scholar 

  • Calam J, Bojarski JC, Springer CJ (1987) Raw soya-bean flour increases cholecystokinin release in man. Br J Nutr 58:175–179

    Article  PubMed  CAS  Google Scholar 

  • Chai Q, Krag S, Miner JH, Nyengaard JR, Chai S, Wogensen L (2003) TGF-beta1 induces aberrant laminin chain and collagen type IV isotype expression in the glomerular basement membrane. Nephron Exp Nephrol 94:e123–e136

    Article  PubMed  CAS  Google Scholar 

  • Dandapani SV, Pollak MR (2006) The glomerular filter: biologic and genetic complexity. Kidney Int 70:980–982

    Article  PubMed  CAS  Google Scholar 

  • de Weerth A, Jonas L, Schade R, Schöneberg T, Wolf G, Pace A, Kirchhoff F, Schulz M, Heinig T, Greten H, von Schrenck T (1998) Gastrin/cholecystokinin type B receptors in the kidney: molecular, pharmacological, functional characterization, and localization. Eur J Clin Invest 28:592–601

    Article  PubMed  Google Scholar 

  • Farquhar MG (2006) The glomerular basement membrane: not gone, just forgotten. J Clin Invest 116:2090–2093

    Article  PubMed  CAS  Google Scholar 

  • Hasselbacher K, Wiggins RC, Matejas V, Hinkes BG, Mucha B, Hoskins BE, Ozaltin F, Nurnberg G, Becker C, Hangan D, Pohl M, Kuwertz-Broking E, Griebel M, Schumacher V, Royer-Pokora B, Bakkaloglu A, Nurnberg P, Zenker M, Hildebrandt F (2006) Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2-associated disorders. Kidney Int 70:1008–1012

    Article  PubMed  CAS  Google Scholar 

  • Jarad G, Cunningham J, Shaw AS, Miner JH (2006) Proteinuria precedes podocyte abnormalities in Lamb2−/− mice, implicating the glomerular basement membrane as an albumin barrier. J Clin Invest 116:2272–2279

    Article  PubMed  CAS  Google Scholar 

  • Kurrikoff K, Kõks S, Matsui T, Bourin M, Aunapuu M, Arend A, Vasar E (2004) Deletion of the CCK2 receptor gene reduces mechanical sensitivity and abolishes the development of hyperalgesia in mononeuropathic mice. Eur J Neurosci 20:1577–1586

    Article  PubMed  Google Scholar 

  • Laurila P, Leivo I (1993) Basement membrane and interstitial matrix components form separate matrices in heterokaryons of PYS-2 cells and fibroblasts. J Cell Sci 104:59–68

    PubMed  CAS  Google Scholar 

  • Lay JM, Jenkins C, Friis-Hansen L, Samuelson LC (2000) Structure and developmental expression of the mouse CCK-B receptor gene. Biochem Biophys Res Commun 272:837–842

    Article  PubMed  CAS  Google Scholar 

  • Miner JH (1999) Renal basement membrane components. Kidney Int 56:2016–2024

    Article  PubMed  CAS  Google Scholar 

  • Miner JH (2003) A molecular look at the glomerular barrier. Nephron Exp Nephrol 94:e119–e122

    Article  PubMed  Google Scholar 

  • Miner JH, Yurchenco PD (2004) Laminin functions in tissue morphogenesis. Annu Rev Cell Dev Biol 20:255–284

    Article  PubMed  CAS  Google Scholar 

  • Morino P, Herrera-Marschitz M, Castel MN, Ungerstedt U, Varro A, Dockray G, Hokfelt T (1994) Cholecystokinin in cortico-striatal neurons in the rat: immunohistochemical studies at the light and electron microscopical level. Eur J Neurosci 6:681–692

    Article  PubMed  CAS  Google Scholar 

  • Santos NC, Castanho MA (2004) An overview of the biophysical applications of atomic force microscopy. Biophys Chem 107:133–149

    Article  PubMed  CAS  Google Scholar 

  • Sasaki T, Mann K, Miner JH, Miosge N, Timpl R (2002) Domain IV of mouse laminin beta1 and beta2 chains. Eur J Biochem 269:431–442

    Article  PubMed  CAS  Google Scholar 

  • Schaer JC, Reubi JC (1999) High gastrin and cholecystokinin (CCK) gene expression in human neuronal, renal, and myogenic stem cell tumors: comparison with CCK-A and CCK-B receptor contents. J Clin Endocrin Metab 84:233–239

    Article  CAS  Google Scholar 

  • Shigehara T, Zaragoza C, Kitiyakara C, Takahashi H, Lu H, Moeller M, Holzman LB, Kopp JB (2003) Inducible podocyte-specific gene expression in transgenic mice. J Am Soc Nephrol 14:1998–2003

    PubMed  CAS  Google Scholar 

  • von Schrenck T, Ahrens M, de Weerth A, Bobrowski C, Wolf G, Jonas L, Jocks T, Schulz M, Blaker M, Neumaier M, Stahl RA (2000) CCKB/gastrin receptors mediate changes in sodium and potassium absorption in the isolated perfused rat kidney. Kidney Int 58:995–1003

    Article  Google Scholar 

  • Wank SA (1995) Cholecystokinin receptors. Am J Physiol 269:G628–G640

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by targeted financing under project No. 0182688s05 from the Estonian Ministry of Education and Science and by the grant 7301 from the Estonian Science Foundation. The authors are grateful to Mr. Kristjan Saal for skillful support for AFM images.

Author information

Authors and Affiliations

  1. Department of Anatomy, Faculty of Medicine, University of Tartu, Ravila 19, Biomedicum, Tartu, 50411, Estonia

    Marina Aunapuu, Peeter Roosaar & Andres Arend

  2. Department of Morphology, Estonian University of Life Sciences, Fr. Kreutzwaldi 62, Tartu, 51014, Estonia

    Tõnu Järveots

  3. Department of Physiology, University of Tartu, Ravila 19, Biomedicum, Tartu, 50411, Estonia

    Kaido Kurrikoff, Sulev Kõks & Eero Vasar

Authors
  1. Marina Aunapuu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peeter Roosaar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tõnu Järveots
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kaido Kurrikoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sulev Kõks
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eero Vasar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Andres Arend
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marina Aunapuu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aunapuu, M., Roosaar, P., Järveots, T. et al. Altered renal morphology in transgenic mice with cholecystokinin overexpression. Transgenic Res 17, 1079–1089 (2008). https://doi.org/10.1007/s11248-008-9204-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11248-008-9204-5

Keywords

Search

Navigation