Effect of tissue factor pathway inhibitor on apoptosis of rat mesangial cells and Fas and bcl-2 expression.
- Author:
Yi-feng LIN
1
;
Duan MA
;
Wang LIANG
;
Tao JIANG
;
Zhong-hua ZHAO
;
Nong ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Apoptosis; drug effects; physiology; Caspase 3; metabolism; Cells, Cultured; drug effects; DNA Fragmentation; Flow Cytometry; Humans; Lipoproteins; metabolism; pharmacology; Mesangial Cells; cytology; drug effects; enzymology; metabolism; Peptides; pharmacology; Rats; bcl-Associated Death Protein; metabolism; pharmacology
- From: Chinese Journal of Pathology 2008;37(11):754-759
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the biological impact and mechanism of recombinant tissue factor pathway inhibitor (rTFPI) on apoptosis of rat kidney mesangial cells (MsC).
METHODSTFPI expression in human glomerular minor lesion (GML), mesangial proliferative glomerulonephritis (MPGN) and cultured rat MsC was detected using immunohistochemistry and immunofluorescence, respectively. Rat MsC were incubated with rTFPI and its variant peptides. Morphological changes of apoptosis were investigated by Hoechst 33258 and the apoptotic rate was assessed by flow cytometry. DNA fragmentation and effect of rTFPI on expression of caspase-3, Fas and bcl-2 were studied using gel electrophoresis and Western blot respectively.
RESULTSThe expression of TFPI in MPGN was higher than that in GML. TFPI was expressed in cultured rat mesangial cells. Apoptosis of MsC was induced by rTFPI, especially by its C-termianl, in a dose- and time-dependent manner. Apoptosis ratios of MsC treated with rTFPI were 2.1, 3.0 and 4.9 times more than control, respectively. Expression of gene caspase-3 and Fas was up-regulated in a dose-dependent manner wherease bcl-2 expression did not show any changes.
CONCLUSIONrTFPI induces apoptosis in cultured rat mesangial cells by its C-terminal possibly via Fas/FasL pathway.