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Immunohistochemical characterization of fibroblast subpopulations in normal peritoneal tissue and in peritoneal dialysis-induced fibrosis

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Abstract

Peritoneal fibrosis is one of the most common morphological changes observed in continuous ambulatory peritoneal dialysis (CAPD) patients. Both resident fibroblasts and new fibroblast-like cells derived from the mesothelium by epithelial-to-mesenchymal transition are the main cells involved fibrogenesis. In order to establish markers of peritoneal impairment and pathogenic clues to explain the fibrogenic process, we conducted an immunohistochemical study focused on peritoneal fibroblasts. Parietal peritoneal biopsies were collected from four patient groups: normal controls (n=15), non-CAPD uremic patients (n=17), uremic patients on CAPD (n=27) and non-renal patients with inguinal hernia (n=12). To study myofibroblastic conversion of mesothelial cells, α-smooth muscle actin (SMA), desmin, cytokeratins and E-cadherin were analyzed. The expression of CD34 by fibroblasts was also analyzed. Fibroblasts from controls and non-CAPD uremic patients showed expression of CD34, but no myofibroblastic or mesothelial markers. The opposite pattern was present during CAPD-related fibrosis. Expression of cytokeratins and E-cadherin by fibroblast-like cells and α-SMA by mesothelial and stromal cells supports that mesothelial-to-myofibroblast transition occurs during CAPD. Loss of CD34 expression correlated with the degree of peritoneal fibrosis. The immunophenotype of fibroblasts varies during the progression of fibrosis. Myofibroblasts seem to derive from both activation of resident fibroblasts and local conversion of mesothelial cells.

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Acknowledgements

We would like to thank the surgeons and nephrology nurses involved in the peritoneal biopsy performance and manipulation. We also thank M. Angeles Cuevas and Norma Freire for their technical assistance on immunohistochemical studies. Grants SAF 2001–0305 from Ministerio de Ciencia y Tecnología to M.L-C, FIS 01/0063–02 from Ministerio de Sanidad y Consumo to R.S. We are indebted to Fresenius Medical Care for the provision of an educational grant to L.S.A.

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Authors and Affiliations

  1. Department of Pathology, University Hospital, Donantes de sangres s/n, 19002, Guadalajara, Spain

    José A. Jiménez-Heffernan

  2. University of Alcalá de Henares, Madrid, Spain

    José A. Jiménez-Heffernan

  3. Department of Nephrology, University Hospital La Princesa, Madrid, Spain

    Abelardo Aguilera, José A. Sánchez-Tomero, Vicente Álvarez & Rafael Selgas

  4. Department of Molecular Biology, Hospital La Princesa, Madrid, Spain

    Luiz S. Aroeira, Enrique Lara-Pezzi, Marta Ramírez & Manuel López-Cabrera

  5. Department of Nephrology, University Hospital La Paz, Madrid, Spain

    M. Auxiliadora Bajo & Gloria del Peso

  6. Department of Pathology, Hospital La Princesa, Madrid, Spain

    Carlos Gamallo

  7. “Grupo de Estudios Peritoneales de Madrid”, Instituto Reina Sofia de Investigaciones Nefrológicas (FRIAT), Spain

    José A. Jiménez-Heffernan, Abelardo Aguilera, Luiz S. Aroeira, Enrique Lara-Pezzi, M. Auxiliadora Bajo, Gloria del Peso, Marta Ramírez, Carlos Gamallo, José A. Sánchez-Tomero, Vicente Álvarez, Manuel López-Cabrera & Rafael Selgas

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  1. José A. Jiménez-Heffernan
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  2. Abelardo Aguilera
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  3. Luiz S. Aroeira
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  4. Enrique Lara-Pezzi
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  5. M. Auxiliadora Bajo
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  8. Carlos Gamallo
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  9. José A. Sánchez-Tomero
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  10. Vicente Álvarez
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  11. Manuel López-Cabrera
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  12. Rafael Selgas
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Corresponding author

Correspondence to José A. Jiménez-Heffernan.

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Manuel López-Cabrera and Rafael Selgas contributed equally to the article.

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Jiménez-Heffernan, J.A., Aguilera, A., Aroeira, L.S. et al. Immunohistochemical characterization of fibroblast subpopulations in normal peritoneal tissue and in peritoneal dialysis-induced fibrosis. Virchows Arch 444, 247–256 (2004). https://doi.org/10.1007/s00428-003-0963-3

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  • DOI: https://doi.org/10.1007/s00428-003-0963-3

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