PENTOXIFYLLINE 預防腹膜纖維化之基礎研究
Date Issued
2001
Date
2001
Author(s)
洪冠予
DOI
892314B002508
Abstract
Peritoneal matrix accumulation is characteristics of encapsulating peritoneal sclerosis
(EPS), which is a serious complication in long-term peritoneal dialysis (PD) patients. We
previously had reported that TGF-b stimulates expression of type I and III collagen mRNA in
cultured HPMC, and was attenuated by pentoxifylline (PTX). The SMAD family and the
mitogen-activated protein kinase (MAPK) (ERK1/2, JNK and p38 HOG ) pathways have been
shown to participate in TGF-b signaling. However, the intracellular signaling downstream to
TGF-b remains undetermined in HPMC. In this study, we explored these signaling pathways
in HPMC, and investigated the molecular mechanisms involved in the inhibitory effects of
PTX on TGF-b induced collagen gene expression in HPMC.
HPMC was cultured from human omentum by an enzyme digestion method. Expression
of collagen a1(I) mRNA was determined by northern blotting. The SMAD proteins and the
MAPK kinase activity were determined by Western blotting.
TGF-b-stimulated collagen a1(I) mRNA expression of HPMC was inhibited by PTX. The Smad2, ERK1/2 and p38HOG pathways were activated in response to TGF-b. However,
TGF-b displayed no activation of the JNK pathway in HPMC. Addition of PD98059 and 2
SB203580, which blocked activation of ERK1/2 and p38 HOG MAPK respectively, suppressed
TGF-b-induced collagen a1(I) mRNA expression. At concentration that inhibited collagen
gene expression, PTX suppressed ERK1/2 and p38 HOG MAPK activation by TGF-b. In
contrast, PTX had no effect on TGF-b-induced activation of Smad2, under the same
concentration.
PTX inhibits TGF-b-induced collagen gene expression in HPMC through modulations of
the ERK1/2 and p38 HOG MAPK pathways. Our study of PTX may provide therapeutic basis
for clinical applications in prevention of EPS.
Subjects
encapsulating peritoneal sclerosis
mesothelial cell
signal
transduction
transduction
Publisher
臺北市：國立臺灣大學醫學院內科
Type
report
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