期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 126, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2023.111261
关键词
Liver fibrosis; EphB1/2; Tyrosine kinase inhibitor; Tetracyclines
The combination of tetracycline antibiotics, demeclocycline (D), chlortetracycline (C), and minocycline (M), showed therapeutic potential against liver fibrosis by inhibiting the activation of hepatic stellate cells and the MAPK signaling. This study suggests that tetracyclines may be repurposed for the treatment of liver fibrosis.
Eph receptor tyrosine kinase EphB1/2 contributes to the development of liver fibrosis, suggesting the rationale that EphB1/2 inhibitors may be effective in liver fibrosis therapy. Since tetracycline antibiotics were recently demonstrated as EphB kinase inhibitors, in present study we investigated their therapeutic potential against liver fibrosis. Our results showed that the tetracycline combination of demeclocycline (D), chlortetracycline (C), and minocycline (M) inhibited the activation of hepatic stellate cells (HSCs) in vitro and alleviated CCl4-induced animal model of liver fibrosis in vivo. Mechanistically, DCM combination inhibited EphB1/2 phosphorylation and subsequent activation of the MAPK signaling. Moreover, we found that short-term and low-dose DCM combination treatment decreased tissue inflammation and improved liver fibrosis in mice. Thus, our study indicates that tetracyclines may be repurposed for the treatment of liver fibrosis.
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