Immunohistochemical characterization of fibroblast subpopulations in normal peritoneal tissue and in peritoneal dialysis-induced fibrosis.
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, alpha-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 alpha-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.
Jiménez-Heffernan
José A
JA
Department of Pathology, University Hospital, Donantes de sangres s/n, 19002, Guadalajara, Spain. jjheffernan@yahoo.com
Aguilera
Abelardo
A
Aroeira
Luiz S
LS
Lara-Pezzi
Enrique
E
Bajo
M Auxiliadora
MA
del Peso
Gloria
G
Ramírez
Marta
M
Gamallo
Carlos
C
Sánchez-Tomero
José A
JA
Alvarez
Vicente
V
López-Cabrera
Manuel
M
Selgas
Rafael
R
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D015820:Cadherins / Q000032:analysis; D004848:Epithelium / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000737:chemistry* / Q000473:pathology*; D005355:Fibrosis / Q000209:etiology; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D007633:Keratins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects*; D010537:Peritoneum / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014511:Uremia / Q000473:pathology
D018952:Antigens, CD34; D015820:Cadherins; D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D007633:Keratins