Rosiglitazone抑制高糖促進細胞外間質堆積之作用機轉
Date Issued
2003
Date
2003
Author(s)
吳寬墩
DOI
912314B002336
Abstract
Background. Glomerulosclerosis is a central pathologic feature of progressive renal diseases.
Mesangial cell proliferation and extracellular matrix (ECM) deposition are regarded as main
processes predisposing to glomerulosclerosis. The peroxisome proliferator-activated receptor γ
(PPAR γ ) is a member of nuclear receptor superfamily that regulates fat-cell differentiation and
glucose homeostasis and is the molecular target of a class of insulin-sensitizing agents used for the
management of type II diabetes mellitus. Thiazolidinedione (TZD), a synthetic ligand of PPAR γ ,was
shown to ameliorate mesangial expansion in vivo. Thus, we investigated the effect of PPAR γ ligands
in inhibiting cell proliferation and ECM gene expression of rat mesangial cells (RMCs) in vitro.
Methods. RMCs were cultured from Sprague-Dawley rats by a modified enzyme digestion method.
Cell proliferation was measured by the methyltetrazolium assay. Cell-cycle distribution of RMC was
analyzed by flow cytometry. Expression of type I (α 1) collagen, fibronectin and connective tissue
growth factor (CTGF) mRNA level were analyzed by Northern blotting.
Results. Treatment of cultured-RMCs with ligands for PPAR γ: [rosiglitazone (RSG), 1 ~50 µM or
15-deoxy-delta 12, 14 -prostaglandin J2 (15d-PGJ2), 1 ~10 µM] inhibited serum and platelet-derived
growth factor (PDGF)-stimulated RMCs proliferation without affecting the cell viability. The PPAR γ
activation suppressed PDGF-stimulated RMCs proliferation by cell-cycle arrest at the G1 phase.
PPAR agonists suppressed serum and transforming growth factor-β (TGF-β )-induced extracellular
matrix gene and CTGF gene expression in RMCs cultures.
Conclusions. PPAR γ ligands, RSG and 15d-PGJ2, inhibit RMC proliferation, type I (α 1) collagen,
fibronectin and CTGF mRNA expression. These results indicate that PPAR γ ligands have
therapeutic potential in progressive renal disease.
Subjects
peroxisome proliferator-activated receptor γ
rat mesangial cell
cell proliferation
cell
cycle
cycle
extracellular matrix
connective tissue growth factor
glomeruloscleroris
SDGs
Publisher
臺北市：國立臺灣大學醫學院內科
Type
report
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