ReferenceID 5251
Fisetin reduces the senescent tubular epithelial cell burden and also inhibits proliferative fibroblasts in murine lupus nephritis
Front Immunol
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
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Record Fields
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- Reference Id
- 5251
- Evidence Id
- 21841
- Core Evidence Id
- 21841
- Source Reference Id
- 3770
- Herb2 Reference Id
- HBREF004567
- Subject Paper Key
- HBIN026506_36466895
- Pubmed Id
- 36466895
- Doi
- 10.3389/fimmu.2022.960601
- Paper Title
- Fisetin reduces the senescent tubular epithelial cell burden and also inhibits proliferative fibroblasts in murine lupus nephritis
- Paper 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 β (TGF-β). TGF-β stimulation induced senescence of NRK-52E renal TECs and proliferation of NRK-49F renal fibroblasts, suggesting that TGF-β 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.
- Journal
- Front Immunol
- Publish Year
- 2022
- Experiment Subject
- mouse; patient; nrk-49f renal fibroblasts; nrk-52e renal tecs
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Chronic Autoimmune Inflammatory Disease; Chronic Inflammation; Lupus Nephritis; Systemic Lupus Erythematosus; Attenuated Kidney Fibrosis; Ln Pathologies
- Paper Title Cn
- Paper Title En
- Fisetin reduces the senescent tubular epithelial cell burden and also inhibits proliferative fibroblasts in murine lupus nephritis
- Bilingual Status
- semi_complete