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AAA-ATPase p97 suppresses apoptotic and autophagy-associated cell death in rheumatoid arthritis synovial fibroblasts
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| Title: | AAA-ATPase p97 suppresses apoptotic and autophagy-associated cell death in rheumatoid arthritis synovial fibroblasts |
| Authors: | Kato, Masaru Browse this author →KAKEN DB | | Ospelt, Caroline Browse this author | | Kolling, Christoph Browse this author | | Shimizu, Tomohiro Browse this author | | Kono, Michihito Browse this author | | Yasuda, Shinsuke Browse this author →KAKEN DB | | Michel, Beat A Browse this author | | Gay, Renate E Browse this author | | Gay, Steffen Browse this author | | Klein, Kerstin Browse this author | | Atsumi, Tatsuya Browse this author →KAKEN DB |
| Keywords: | p97 | | histone deacetylase 6 | | polyubiquitin | | cell death | | autophagy |
| Issue Date: | 27-Sep-2016 |
| Publisher: | Impact Journals |
| Journal Title: | Oncotarget |
| Volume: | 7 |
| Issue: | 39 |
| Start Page: | 64221 |
| End Page: | 64232 |
| Publisher DOI: | 10.18632/oncotarget.11890 |
| Abstract: | Valosin containing protein (p97) is a chaperone implicated in a large number of biological processes including endoplasmic reticulum (ER)-associated protein degradation and autophagy. Silencing of p97 in rheumatoid arthritis (RA) synovial fibroblasts (RASFs) increased the amount of polyubiquitinated proteins, whereas silencing of its interaction partner histone deacetylase 6 (HDAC6) had no effect. Furthermore, silencing of p97 in RASFs increased not only rates of apoptotic cell death induced by TRAIL but also induced an autophagy-associated cell death during ER stress that was accompanied by the formation of polyubiquitinated protein aggregates and large vacuoles. Finally, we demonstrated an anti-arthritic effect of siRNAs targeting p97 in collagen-induced arthritis in rats. Our data indicate that p97 may be a new potential target in the treatment of RA. |
| Rights: | https://creativecommons.org/licenses/by/3.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/64006 |
| Appears in Collections: | 北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 加藤 将
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