蛋白激酶B
PI3K/AKT/mTOR通路
激酶
信号转导
转化生长因子
化学
纤维化
内分泌学
磷酸化
内科学
癌症研究
医学
生物化学
作者
Xin Li,Zhou-long zhang,Huifen Wang
标识
DOI:10.1016/j.biopha.2017.06.002
摘要
Fusaric acid (FA) is a novel compound derived from a class of nicotinic acid derivatives, exhibiting activity against cancers. However, its role in regulating cardiac injury is limited. Our study was aimed to investigate the role and the underlying molecular mechanism of FA in heart fibrosis and hypertrophy. Isoproterenol (ISP) was used to induce cardiac fibrosis and hypertrophy in vitro and in vivo. FA administration ameliorated hypertrophy by reducing atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β −myosin heavy chain (β-MHC) in vitro and in vivo. Additionally, FA reduced collagen accumulation and fibrosis-related signals, including α- smooth muscle actin (α-SMA), Collagen type I and Collagen type III. Transforming growth factor-β1 (TGF-β1)/SMADs and mitogen-activated protein kinases (MAPKs), including p38, extracellular signal regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), signalling pathways were highly activated for ISP induction, which were prevented due to FA administration. Further, FA suppressed ISP-induced PI3K/AKT activity in a dose dependent manner. Of note, FA-reduced MAPKs phosphorylation was associated with phosphoinositide 3-Kinase (PI3K)/Protein kinase B (AKT) activity caused by ISP. However, PI3K/AKT activation showed no effects on TGF-β1/SMADs expression in FA-treated cells after ISP exposure. Together, FA might be an effective candidate agent for preventing cardiac fibrosis by modulating TGF-β1/SMADs and PI3K/AKT signalling pathways.
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