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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Health Sciences / Faculty of Health Sciences >
Peer-reviewed Journal Articles, etc >
Fisetin reduces the senescent tubular epithelial cell burden and also inhibits proliferative fibroblasts in murine lupus nephritis
| Title: | Fisetin reduces the senescent tubular epithelial cell burden and also inhibits proliferative fibroblasts in murine lupus nephritis |
| Authors: | Ijima, Shogo Browse this author | | Saito, Yuki Browse this author →KAKEN DB | | Nagaoka, Kentaro Browse this author | | Yamamoto, Sena Browse this author | | Sato, Tsukasa Browse this author | | Miura, Norihiro Browse this author | | Iwamoto, Taiki Browse this author | | Miyajima, Maki Browse this author →KAKEN DB | | Chikenji, Takako S. Browse this author →KAKEN DB |
| Keywords: | systemic lupus erythematosus (SLE) | | lupus nephritis (LN) | | senescence | | transforming growth factor beta (TGF-beta) | | p15(INK4B) | | senolytic agent | | fisetin |
| Issue Date: | 17-Nov-2022 |
| Publisher: | Frontiers Media |
| Journal Title: | Frontiers in immunology |
| Volume: | 13 |
| Start Page: | 960601 |
| Publisher DOI: | 10.3389/fimmu.2022.960601 |
| PMID: | 36466895 |
| Abstract: | Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease characterized by the involvement of multiple organs. Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in SLE patients. Hence, designing effective drugs is pivotal for treating individuals with LN. Fisetin plays a senolytic role by specifically eliminating senescent cells, inhibiting cell proliferation, and exerting anti-inflammatory, anti-oxidant, and anti-tumorigenic effects. However, limited research has been conducted on the utility and therapeutic mechanisms of fisetin in chronic inflammation. Similarly, whether the effects of fisetin depend on cell type remains unclear. In this study, we found that LN-prone MRL/lpr mice demonstrated accumulation of Ki-67-positive myofibroblasts and p15(INK4B)-positive senescent tubular epithelial cells (TECs) that highly expressed transforming growth factor beta (TGF-beta). TGF-beta stimulation induced senescence of NRK-52E renal TECs and proliferation of NRK-49F renal fibroblasts, suggesting that TGF-beta promotes senescence and proliferation in a cell type-dependent manner, which is inhibited by fisetin treatment in vitro. Furthermore, fisetin treatment in vivo reduced the number of senescent TECs and myofibroblasts, which attenuated kidney fibrosis, reduced senescence-associated secretory phenotype (SASP) expression, and increased TEC proliferation. These data suggest that the effects of fisetin vary depending on the cell type and may have therapeutic effects in complex and diverse LN pathologies. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/88112 |
| Appears in Collections: | 保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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