Citation: Wei Lei, Fukui Shen, Nianwei Chang, Lin Niu, Yuanyuan Hou, Boli Zhang, Min Jiang, Gang Bai. Chemical proteomics reveals ligustilide targets SMAD3, inhibiting collagen synthesis in aortic endothelial cells[J]. Chinese Chemical Letters, ;2021, 32(1): 190-193. doi: 10.1016/j.cclet.2020.10.049 shu

Chemical proteomics reveals ligustilide targets SMAD3, inhibiting collagen synthesis in aortic endothelial cells

Wei Lei ^{a, b} ,
Fukui Shen ^a ,
Nianwei Chang ^b ,
Lin Niu ^b ,
Yuanyuan Hou ^a ,
Boli Zhang ^b ,
Min Jiang ^{a, *,} ,
Gang Bai ^{a, *,}

a.
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China
b.
Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China

minjiang@nankai.edu.cn

gangbai@nankai.edu.cn

Received Date: 17 September 2020
Revised Date: 12 October 2020
Accepted Date: 31 October 2020
Available Online: 3 November 2020

Figures(4)

Atherosclerosis is a persistent inflammatory state, while vascular endothelial fibrosis is one of the primary causes of atherosclerosis development. Although ligustilide (Lig) was shown to exert obvious antiatherogenic effects in previous studies, its precise mechanism has not been deeply discussed. In this paper, we designed a Lig-derived photoaffinity labelling (PAL) probe to identify potential therapeutic targets of Lig via chemical proteomics approach. Mothers against decapentaplegic homologue 3 (SMAD3), a signal transmitter of transforming growth factor-β (TGF-β) which promotes the development of vascular fibrosis, was identified as a potential target of Lig. Lig suppressed the phosphorylation and nuclear translocation of SMAD3 by blocking the interaction between SMAD3 and TGF-β receptor 1, thereby inhibiting the collagen synthesis process. Hence, developing a novel SMAD3 inhibitor may present a promising therapeutic option for preventing vascular fibrosis.
- Ligustilide,
- SMAD3,
- Collagen synthesis,
- Chemical proteomics,
- Photoaffinity labelling
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