TAK1 inhibition attenuates both inflammation and fibrosis in experimental pneumoconiosis
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AbstractPneumoconiosis, caused by inhalation of mineral dusts, is a major occupational disease worldwide. Currently, there are no effective drugs owing to a lack of potential therapeutic targets during either the inflammation or fibrosis molecular events in pneumoconiosis. Here, we performed microarrays to identify aberrantly expressed genes in the above molecular events in vitro and found a hub gene transforming growth factor-β-activated kinase 1 (TAK1), which was highly expressed and activated in pneumoconiosis patients as well as silica-exposed rats with experimental pneumoconiosis. Genetic modulation of TAK1 by CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9, RNA interference and overexpression indicated the important role of TAK1 in both inflammation and fibrosis in experimental pneumoconiosis. To achieve pharmacological TAK1 inhibition, we virtually screened out a natural product resveratrol, which targeted TAK1 at both N161 and A107 residues, and significantly inhibited TAK1 activation to attenuate inflammation and fibrosis in vitro. Consistently, in vivo prevention and intervention studies showed that resveratrol could inhibit pulmonary inflammation and fibrosis in silica-exposed rats.
All Author(s) ListJie Li, Chao Liang, Zong-Kang Zhang, Xiaohua Pan, Songlin Peng, Wing-Sze Lee, Aiping Lu, Zhixiu Lin, Ge Zhang, Wing-Nang Leung, Bao-Ting Zhang
Journal nameCell Discovery
Year2017
Month7
Day11
Volume Number3
Pages17023
ISSN2056-5968
LanguagesEnglish-United Kingdom

Last updated on 2020-18-10 at 02:37