Carnosic Acid Alleviates BDL-Induced Liver Fibrosis through miR-29b-3p-Mediated Inhibition of the High-Mobility Group Box 1/Toll-Like Receptor 4 Signaling Pathway in Rats.
Carnosic Acid Alleviates BDL-Induced Liver Fibrosis through miR-29b-3p-Mediated Inhibition of the High-Mobility Group Box 1/Toll-Like Receptor 4 Signaling Pathway in Rats.
复制标题
鼠尾草酸通过 miR-29b-3p 介导的高迁移率族盒 1/Toll 样受体 4 信号通路抑制减轻 BDL 诱导的肝纤维化
DOI：
10.3389/fphar.2017.00976
复制
发表时间：
2017
影响因子：
5.6
通讯作者：
Yao J
中科院分区：
文献类型：
--
作者：
Zhang S;Wang Z;Zhu J;Xu T;Zhao Y;Zhao H;Tang F;Li Z;Zhou J;Gao D;Tian X;Yao J
肝纤维化反映了向肝癌或肝硬化的进展。近年来的研究表明，高迁移率族蛋白1（HMGB 1）在肝损伤和肝纤维化中起重要作用。鼠尾草酸（CA），一种从迷迭香中提取的化合物，已被报道可以减轻酒精性和非酒精性脂肪肝损伤。CA还可以减轻肾纤维化。我们假设CA可能通过HMGB 1相关途径发挥抗肝纤维化特性，本研究的结果表明，CA治疗显著保护胆管结扎（BDL）大鼠模型免受肝纤维化。CA降低肝脏α-平滑肌肌动蛋白（α-SMA）和胶原1（Col-1）的表达。更重要的是，我们发现CA改善了由BDL引起的HMGB 1和Toll样受体4（TLR 4）的增加，并抑制了纤维化肝脏中NF-κB p65核转位。CA通过抑制HMGB 1/TLR 4信号通路抑制LX 2细胞活化。此外，miR-29 b-3 p降低HMGB 1表达，双荧光素酶测定验证了这些结果。CA下调HMGB 1的表达，抑制LX 2细胞的活化，并能被miR-29 b-3 p显著抵消，提示CA对HMGB 1表达的抑制可能是miR-29 b-3 p依赖性的。综上所述，CA可调控miR-29 B-3 p/HMGB 1/TLR 4/NF-κB信号通路在肝纤维化中发挥重要作用，提示CA可能是一种有前景的肝纤维化治疗药物。
Fibrosis reflects a progression to liver cancer or cirrhosis of the liver. Recent studies have shown that high-mobility group box-1 (HMGB1) plays a major role in hepatic injury and fibrosis. Carnosic acid (CA), a compound extracted from rosemary, has been reported to alleviate alcoholic and non-alcoholic fatty liver injury. CA can also alleviate renal fibrosis. We hypothesized that CA might exert anti-liver fibrosis properties through an HMGB1-related pathway, and the results of the present study showed that CA treatment significantly protected against hepatic fibrosis in a bile duct ligation (BDL) rat model. CA reduced the liver expression of α-smooth muscle actin (α-SMA) and collagen 1 (Col-1). Importantly, we found that CA ameliorated the increase in HMGB1 and Toll-like receptor 4 (TLR4) caused by BDL, and inhibited NF-κB p65 nuclear translocation in fibrotic livers. In vitro, CA inhibited LX2 cell activation by inhibiting HMGB1/TLR4 signaling pathway. Furthermore, miR-29b-3p decreased HMGB1 expression, and a dual-luciferase assay validated these results. Moreover, CA down-regulated HMGB1 and inhibited LX2 cell activation, and these effects were significantly counteracted by antago-miR-29b-3p, indicating that the CA-mediated inhibition of HMGB1 expression might be miR-29b-3p dependent. Collectively, the results demonstrate that a miR-29b-3p/HMGB1/TLR4/NF-κB signaling pathway, which can be modulated by CA, is important in liver fibrosis, and indicate that CA might be a prospective therapeutic drug for liver fibrosis.
登录
查看更多内容
DOI：
10.1152/ajplung.00075.2007
发表时间：
2007-12-01
影响因子：
4.9
作者：
He, Mei;Kubo, Hiroshi;Yamaya, Mutsuo
通讯作者：
Yamaya, Mutsuo
影响因子：
24.5
作者：
Mencin A;Kluwe J;Schwabe RF
通讯作者：
Schwabe RF
影响因子：
2.4
作者：
Park MY;Mun ST
通讯作者：
Mun ST
DOI：
10.1165/rcmb.2007-0330oc
发表时间：
2008-10-01
影响因子：
6.4
作者：
Hamada, Naoki;Maeyama, Takashige;Nakanishi, Yoichi
通讯作者：
Nakanishi, Yoichi
DOI：
10.1164/rccm.200712-1894oc
发表时间：
2008-10-15
影响因子：
24.7
作者：
Rowe, Steven M.;Jackson, Patricia L.;Blalock, J. Edwin
通讯作者：
Blalock, J. Edwin