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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Pharmacol
2017 ; 8
(ä): 264
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Hydroxysafflor Yellow A Suppresses MRC-5 Cell Activation Induced by TGF-?1 by
Blocking TGF-?1 Binding to T?RII
#MMPMID28553231
Pan R
; Zhang Y
; Zheng M
; Zang B
; Jin M
Front Pharmacol
2017[]; 8
(ä): 264
PMID28553231
show ga
Hydroxysafflor yellow A (HSYA) is an active ingredient of Carthamus tinctorius
L.. This study aimed to evaluate the effects of HSYA on transforming growth
factor-?1 (TGF-?1)-induced changes in proliferation, migration, differentiation,
and extracellular matrix accumulation and degradation in human fetal lung
fibroblasts (MRC-5), to explore the mechanisms whereby HSYA may alleviate
pulmonary fibrosis. MRC-5 cells were incubated with various doses of HSYA and/or
the TGF-? receptor type I kinase inhibitor SB431542 and then stimulated with
TGF-?1. Cell proliferation was measured by
3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium
inner salt assay. Cell migration was detected by wound-healing assay. Protein
levels of ?-smooth muscle actin (?-SMA), collagen I ? 1 (COL1A1), and fibronectin
(FN) were measured by immunofluorescence. Protein levels of matrix
metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-1, tissue
inhibitor of matrix metalloproteinase-2, TGF-? type II receptor (T?RII), and
TGF-? type I receptor were detected by western blotting. T?RII knockdown with
siRNA interfered with the inhibitory effect of HSYA on ?-SMA, COL1A1, and FN
expression, and TGF-?1-induced Sma and Mad protein (Smad), and extracellular
signal-regulated kinase/mitogen-activated protein kinase signaling pathway
activation. The antagonistic effect of HSYA on the binding of fluorescein
isothiocyanate-TGF-?1 to MRC-5 cell cytoplasmic receptors was measured by flow
cytometry. HSYA significantly suppressed TGF-?1-induced cell proliferation and
migration. HSYA could antagonize the binding of FITC-TGF-?1 to MRC-5 cell
cytoplasmic receptors. Also HSYA inhibited TGF-?1-activated cell expression of
?-SMA, COL1A1, and FN and phosphorylation level of Smad2, Smad3, and ERK by
targeting T?RII in MRC-5 cells. These findings suggest that T?RII might be the
target responsible for the inhibitory effects of HSYA on TGF-?1-induced
pathological changes in pulmonary fibrosis.