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10.3389/fphar.2017.00264

http://scihub22266oqcxt.onion/10.3389/fphar.2017.00264
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suck abstract from ncbi


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pmid28553231      Front+Pharmacol 2017 ; 8 (ä): ä
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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): ä PMID28553231show 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-tet razolium 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.
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