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Struktur und Funktion der suburothelialen Myofibroblasten in der humanen Harnblase unter normalen und pathologischen Bedingungen

Structure and function of suburothelial myofibroblasts in the human urinary bladder under normal and pathological conditions

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J.N. und M.H. trugen gleichermaßen zu der präsentierten Arbeit bei.

Zusammenfassung

Hintergrund

Bei zahlreichen pathologischen Veränderungen spielen Myofibroblasten eine wesentliche Rolle. Die Aufklärung der Struktur und Funktion sowie der zellulären Plastizität dieses Zelltyps in der Harnblase könnte zu einer neuen Beurteilung der Pathogenese von Harnabflusstörungen führen.

Patienten und Methoden

Harnblasenbiopsien von Tumorpatienten und Patienten mit interstitieller Zystitis wurden immunhistologisch und elektronenmikroskopisch untersucht. Kopplungseigenschaften wurden an kultivierten Myofibroblasten und Detrusormuskelzellen mit Hilfe von Farbstoffinjektion analysiert.

Ergebnisse

Myofibroblasten stehen in engem Kontakt zum suburothelialen Kapillarnetz. Sie exprimieren Cx43 und bilden funktionelle Synzytien. Die Expression von muskarinischen und purinergen Rezeptoren variiert sehr stark. In Farbstoffkopplungsexperimenten fanden wir Unterschiede zu Detrusormyozyten.

Diskussion

Pathologische Expression von glattmuskulärem Aktin und/oder Transdifferenzierung zu glatten Muskelzellen könnten eine Rolle bei der Ätiologie der Dranginkontinenz spielen. Ein mehrstufiges Modell wird als Arbeitshypothese vorgeschlagen.

Abstract

Background

Myofibroblasts play a pivotal role in numerous pathological alterations. Clarification of the structure and function and of the cellular plasticity of this cell type in the bladder may lead to new insights into the pathogenesis of lower urinary tract disorders.

Patients and methods

Bladder biopsies from patients with bladder carcinoma and interstitial cystitis were used to analyse the morphology and receptor expression using confocal immunofluorescence and electron microscopy. Cytokine effects and coupling behavior were tested in cultured myofibroblasts and detrusor smooth muscle cells.

Results

Myofibroblasts are in close contact with the suburothelial capillary network. They express Cx43 and form functional syncytia. The expression of muscarinic and purinergic receptors is highly variable. Dye coupling experiments showed differences to detrusor myocytes.

Conclusions

Upregulation of smooth muscle cell alpha-actin and/or transdifferentiation into smooth muscle cells may contribute to the ethiology of urge incontinence. A multi-step model is presented as a working hypothesis.

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Danksagung

Die Autoren danken Frau A. Weimann und Frau J. Craatz für die hervorragende technische Unterstützung.

Interessenskonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

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Authors and Affiliations

  1. Klinik und Poliklinik für Urologie, Universitätsklinikum Leipzig AöR, Liebigstraße 20, 04103, Leipzig, Deutschland

    J. Neuhaus, M. Heinrich, T. Schwalenberg & J.-U. Stolzenburg

  2. Medizinische Klinik III, Endokrinologische Molekularbiologie, xxx, Deutschland

    N. Schlichting & A. Oberbach

  3. Institut für Anatomie, Universität Leipzig, Leipzig, Deutschland

    G. Fitzl

  4. Institut für Pathologie, Universität Leipzig, Leipzig, Deutschland

    L.-C. Horn

Authors
  1. J. Neuhaus
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  2. M. Heinrich
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  3. N. Schlichting
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  4. A. Oberbach
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  5. G. Fitzl
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  6. T. Schwalenberg
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  7. L.-C. Horn
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  8. J.-U. Stolzenburg
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Corresponding author

Correspondence to J. Neuhaus.

Additional information

Gefördert durch die DFG, Ne425/4–3.

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Neuhaus, J., Heinrich, M., Schlichting, N. et al. Struktur und Funktion der suburothelialen Myofibroblasten in der humanen Harnblase unter normalen und pathologischen Bedingungen. Urologe 46, 1197–1202 (2007). https://doi.org/10.1007/s00120-007-1480-9

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  • DOI: https://doi.org/10.1007/s00120-007-1480-9

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