P150 The Triptryium wilfordii derivative celastrol has anti-fibrotic effects in systemic sclerosis
| Autor: | Andrew Leask, Richard J Stratton, Shiwen Xu, Pratyusha Chitturi |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Rheumatology. 62 |
| ISSN: | 1462-0332 1462-0324 |
| DOI: | 10.1093/rheumatology/kead104.191 |
| Popis: | Background/Aims Scleroderma (systemic sclerosis, SSc) is an autoimmune inflammatory-fibrosis syndrome that damages the skin and internal organs and is considered a prototypic complex fibrotic disease. In SSc, persistently activated myofibroblasts are maintained by an excessive, autocrine mechanotranductive/pro-adhesive signaling loop. Drugs targeting this pathway are therefore of likely therapeutic benefit in SSc. The mechanosensitive transcriptional co-activator, yes activated protein-1 (YAP1), is activated in SSc fibroblasts. The terpenoid plant-derivative celastrol has recently been identified as a YAP inhibitor; however, if celastrol can alleviate SSc fibrosis, and its underlying mechanism of action, is as yet unclear. Methods We cultured age-, sex-, and site-matched human dermal fibroblasts sampled from healthy individuals and patients with early onset ( Results In dermal fibroblasts, celastrol impaired the ability of TGFβ1 to induce an SSc-like pattern of gene expression, including the induction of cellular communication network factor 2 (CCN2), collagen I and TGFβ1 protein (N = 6, all p Conclusion Our data are consistent with the hypothesis that compounds, such as celastrol, that antagonize the YAP pathway warrant further consideration as potential treatments for SSc skin fibrosis. Disclosure A. Leask: Grants/research support; CIHR, NSERC, Arthritis Society of Canada. R.J. Stratton: None. S. Xu: None. P. Chitturi: None. |
| Databáze: | OpenAIRE |
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