Peritoneal fibrosis is a major complication of
continuous ambulatory peritoneal dialysis (
CAPD). The present study tested the hypothesis that
ADP-ribose polymerase-1 (PARP-1) may play a role in peritoneal epithelial-mesenchymal transition and
fibrosis under high
glucose conditions. High
glucose (126 mmol/l)-induced peritoneal EMT and
fibrosis via the PARP-1 mechanism was examined in the primary culture of rat peritoneal mesothelial cells (PMCs) and in the human peritoneal mesothelial cell line (HMrSv5) in the presence or absence of a PARP-1 inhibitor
PJ34 (3x10-6 M) or by knocking down PARP-1 with the PARP-1
siRNA technique. High
glucose significantly increased PARP-1 expression and EMT as demonstrated by de novo expression of a mesenchymal marker α-SMA and loss of epithelial phenotype
E-cadherin by both rat and human PMC, resulting in
peritoneal fibrosis including up-regulation of
plasminogen activator inhibitor-1 (PAI-1),
collagen I, and
fibronectin mRNA and
protein expression. All these fibrotic responses induced by high
glucose were significantly inhibited by the PARP-1 inhibitor
PJ34 (all P<0.05) or by knocking down PARP-1 with the
siRNA technique. Results from this study suggested that high
glucose stimulates peritoneal EMT and
fibrosis via a PARP-1-dependent mechanism, and targeting the PARP-1 may represent an alternative therapeutic potential for
CAPD-related
peritoneal fibrosis.