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2018 ; 41
(6
): 3278-3286
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
Trifluoperazine induces apoptosis through the upregulation of Bax/Bcl?2 and
downregulated phosphorylation of AKT in mesangial cells and improves renal
function in lupus nephritis mice
#MMPMID29568865
Wang B
; Luo Y
; Zhou X
; Li R
Int J Mol Med
2018[Jun]; 41
(6
): 3278-3286
PMID29568865
show ga
The inhibition of mesangial cell (MC) proliferation has become an important
therapy in preventing glomerular proliferation diseases. Trifluoperazine (TFP)
has been reported to inhibit the proliferation of several types of cancer cell,
however, the effects of TFP in renal proliferation diseases remain to be fully
elucidated. The present study examined the effects of TFP on the proliferation of
MCs and quantified cell apoptosis progression in vivo and in vitro. The effects
of various TFP concentrations and treatment durations on cell proliferation and
cell apoptosis in vitro were analyzed using flow cytometry in conjunction with a
Cell Counting kit?8 assay. Cell proliferation in vivo was determined using
hematoxylin and eosin staining and immunohistochemistry of Ki67. The expression
of the two cell apoptosis?related proteins, B?cell lymphoma-2 (Bcl?2) and
Bcl?2?associated X protein (Bax), were estimated using western blot analysis and
immunohistochemistry in vivo and in vitro. TFP?induced phosphatidylinositol
3?kinase (PI3K)/protein kinase B (AKT) signaling pathways were also estimated
using western blot analysis. These results suggested that TFP inhibited MC
proliferation in a dose? and time?dependent manner. It was found that TFP
inhibited the abnormal proliferation of MCs, which was stimulated by 20% fetal
bovine serum in vitro and in lupus MRL/lpr mice. TFP promoted cell apoptosis,
downregulated the expression of Bcl?2 and upregulated the expression of Bax in a
dose?dependent manner at mRNA and protein levels. In addition, TFP inhibited
phosphorylated AKT, potentially leading to the suppressed activation of PI3K/AKT
signaling pathways. TFP treatment significantly decreased the levels of blood
urea nitrogen and serum creatinine, but had no significant effects on the body
weight and liver function of the lupus mice. These results validated and
reinforced the potential of TFP in the treatment of mesangial proliferative
diseases.