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Abstract
Prevention or treatment of peritoneal fibrosing syndrome has become an important issue
in patients on continuous ambulatory peritoneal dialysis (CAPD). Recent evidence has
suggested that mesothelial stem cell proliferation and matrix over-production predispose
the development of peritoneal fibrosis. We investigated whether pentoxifylline (PTX)
affects human peritoneal mesothelial cell (HPMC) growth and collagen synthesis.
HPMC was cultured from human omentum by an enzymic disaggregation method. Cell proliferation
was assayed using a methyltetrazolium uptake method. Cell cycle analysis was performed
by flow cytometry. Collagen synthesis was measured by 3H-proline incorporation into
pepsin-resistant, salt-precipitated collagen. Prostaglandins and cAMP were determined
by enzyme immunoassay. Northern blot analysis was used to determine mRNA expression.
Our data show that PTX inhibited serum-stimulated HPMC growth and collagen synthesis
in a dose-dependent manner. Cell cycle analysis showed that PTX arrested the HPMCs
in the G1 phase. PTX decreased the procollagen alpha1 (I) mRNA expression either stimulated
by serum or transforming growth factor-beta (TGF-beta). PTX did not alter prostaglandins
synthesis but dose-dependently increased intracellular cAMP level. PTX, the same as
3-isobutyl-l-methylxanthine, could potentiate prostaglandin E1 (PGE1) increased cAMP
levels of HPMC. The antimitogenic and antifibrogenic effects of PTX on HPMC were reversed
by N-[2]-((p-Bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide (H-89). Therefore,
the mechanism of these effects may be due to the phospodiesterase inhibitory property
of PTX.
These data suggest that PTX may have a role in treating peritoneal fibrosing syndrome.