PI3K/AKT/mTOR通路
蛋白激酶B
白花丹
SMAD公司
体内
化学
成纤维细胞
细胞生物学
LY294002型
信号转导
癌症研究
生物
体外
生物化学
遗传学
生物技术
作者
Wei Shi,Yuanyuan Fang,Yueming Jiang,Siyang Jiang,Yu Li,Wentao Li,Min Xu,Michael Aschner,Guangnan Liu
出处
期刊:Bioengineered
[Informa]
日期:2021-01-01
卷期号:12 (1): 4475-4488
被引量:5
标识
DOI:10.1080/21655979.2021.1954580
摘要
Traumatic tracheal stenosis (TS) is a serious respiratory disease characterized by hyperplasia of airway granulation. Plumbagin (PLB) is a natural naphthoquinone component with anti-fibrotic properties. This research aimed to explore the roles of PLB in alleviating TS and the underlying mechanisms. For in vitro studies, lung fibroblasts (IMR-90 cells), with/without PLB treatment or TGF-β1 induction, were used. The viability and proliferation of IMR-90 cells were examined by CCK-8 and EdU incorporation assays. The differentiation of IMR-90 cells was assessed by detecting the mRNA and protein expression levels of collagen (COL)-1 and alpha-smooth muscle actin (α-SMA). Besides, immunofluorescence assay was conducted to evaluate the localization of α-SMA in TGF-β1-induced IMR-90 cells. Moreover, the combination of PLB with/without TβRI (SB-431,542), PI3K/Akt (Ly294002) or mTOR (rapamycin) inhibitor was pretreated on IMR-90 cells after TGF-β1 induction. For in vivo studies, a rat model of TS was established. The pathological features and severity of TS were determined by hematoxylin and eosin staining. The protein levels of TGF-β1/Smad and Akt/mTOR pathways were detected for both in vitro and in vivo models. PLB effectively inhibited the proliferation and differentiation of TGF-β1-induced IMR-90 cells, and suppressed TGF-β1/Smad and Akt/mTOR signaling pathways both in vivo and in vitro. Furthermore, PLB reduced the degree of TS in rats. Taken together, our results indicate that PLB regulates lung fibroblast activity and attenuates TS in rats by inhibiting TGF-β1/Smad and Akt/mTOR signaling pathways. In conclusion, this study implies that PLB may serve as a promising therapeutic compound for TS.
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