Treatment effects of the traditional Chinese medicine Shenks in bleomycin-induced lung fibrosis through regulation of TGF-beta/Smad3 signaling and oxidative stress

被引：41

作者：

Chu, Haiyan ^{[1
]}

Shi, Ying ^{[2
,3
]}

Jiang, Shuai ^{[1
]}

Zhong, Qicheng ^{[2
]}

Zhao, Yongqiang ^{[2
]}

Liu, Qingmei ^{[1
]}

Ma, Yanyun ^{[1
]}

Shi, Xiangguang ^{[1
]}

Ding, Weifeng ^{[1
]}

Zhou, Xiaodong ^{[4
]}

Cui, Jimin ^{[2
]}

Jin, Li ^{[1
]}

Guo, Gang ^{[2
]}

Wang, Jiucun ^{[1
,5
]}

机构：

[1] Fudan Univ, Sch Life Sci, Collaborat Innovat Ctr Genet & Dev, State Key Lab Genet Engn, 2005 Songhu Rd, Shanghai 200438, Peoples R China

[2] Hebei Med Univ, Yiling Affiliated Hosp, Dept Rheumatol & Immunol, Shijiazhuang 050091, Peoples R China

[3] Geriatr Hosp Hebei Prov, Dept Tradit Chinese Med, Shijiazhuang 050011, Peoples R China

[4] Univ Texas Hlth Sci Ctr Houston, 6431 Fannin St, Houston, TX 77030 USA

[5] Fudan Univ, Inst Rheumatol Immunol & Allergy, Shanghai 200040, Peoples R China

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

美国国家科学基金会;

关键词：

IDIOPATHIC PULMONARY-FIBROSIS; GROWTH-FACTOR-BETA; PATHOGENESIS; ACTIVATION; DISEASE; CELLS; CYCLOPHOSPHAMIDE; MECHANISMS; DISSECTION; PLACEBO;

D O I：

10.1038/s41598-017-02293-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Pulmonary fibrosis is a kind of devastating interstitial lung disease due to the limited therapeutic strategies. Traditional Chinese medicine (TCM) practices have put forth Shenks as a promising treatment approach. Here, we performed in vivo study and in vitro study to delineate the anti-fibrotic mechanisms behind Shenks treatment for pulmonary fibrosis. We found that regardless of the prophylactic or therapeutic treatment, Shenks was able to attenuate BLM-induced-fibrosis in mice, down regulate extracellular matrix genes expression, and reduce collagen production. The aberrantly high Smad3 phosphorylation levels and SBE activity in TGF-beta-induced fibroblasts were dramatically decreased as a result of Shenks treatment. At the same time, Shenks was able to increase the expression of antioxidant-related genes, including Gclc and Ec-sod, while reduce the transcription levels of oxidative-related genes, such as Rac1 and Nox4 demonstrated by both in vivo and in vitro studies. Further investigations found that Shenks could decrease the oxidative productions of protein (3-nitrotyrosine) and lipid (malondialdehyde) and increase GSH content both in bleomycin treated mouse lungs and TGF-beta stimulated fibroblasts, as well as inhibit the production of ROS stimulated by TGF-beta to fight against oxidative stress. Overall, Shenks inhibited fibrosis by blocking TGF-beta pathway and modulating the oxidant/antioxidant balance.

引用

页数：12

共 45 条

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Therapeutic Potential and Anti-Amyloidosis Mechanisms of Tert-Butylhydroquinone for Alzheimer's Disease [J].