Quercetin Ameliorates Renal Injury and Pyroptosis in Lupus Nephritis through Inhibiting IL-33/ST2 Pathway In Vitro and In Vivo
Lupus nephritis (LN) is a common and serious symptom in patients with systemic lupus erythematosus (SLE). Tubular interstitial fibrosis is a common underlying mechanism in the development of lupus nephritis to end-stage renal failure (ESRD). Quercetin is widely proven to prevent tissue fibrosis. The...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/11/11/2238 |
| _version_ | 1797466070456467456 |
|---|---|
| author | Hsin-Yuan Chen Yi-Fen Chiang Yong-Han Hong Tzong-Ming Shieh Tsui-Chin Huang Mohamed Ali Hsin-Yi Chang Kai-Lee Wang Shih-Min Hsia |
| author_facet | Hsin-Yuan Chen Yi-Fen Chiang Yong-Han Hong Tzong-Ming Shieh Tsui-Chin Huang Mohamed Ali Hsin-Yi Chang Kai-Lee Wang Shih-Min Hsia |
| author_sort | Hsin-Yuan Chen |
| collection | DOAJ |
| description | Lupus nephritis (LN) is a common and serious symptom in patients with systemic lupus erythematosus (SLE). Tubular interstitial fibrosis is a common underlying mechanism in the development of lupus nephritis to end-stage renal failure (ESRD). Quercetin is widely proven to prevent tissue fibrosis. Therefore, the purpose of this study is to investigate the beneficial effects of quercetin on the inhibition of fibrosis and inflammation pathways in in vitro and in vivo lupus nephritis models. In the current study, MRL/lpr mice as animal models, and HK-2 human renal tubular epithelial cells were stimulated by interleukin-33 (IL-33) to mimic the cellular model of lupus nephritis. Immunohistochemical staining, immunoblotting assay, immunofluorescence staining, and quantitative real-time polymerase chain reaction assay were used. The in vivo results showed that quercetin improved the renal function and inhibited both fibrosis- and inflammation-related markers in MRL/lpr mice animal models. The in vitro results indicated that quercetin ameliorated the accumulation of fibrosis- and inflammation-related proteins in IL-33-induced HK-2 cells and improved renal cell pyroptosis via the IL33/ST2 pathway. Overall, quercetin can improve LN-related renal fibrosis and inflammation, which may offer an effective potential therapeutic strategy for lupus nephritis. |
| first_indexed | 2024-03-09T18:31:00Z |
| format | Article |
| id | doaj.art-284ecb25d5454692adf2f7548a5ca1c3 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T18:31:00Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-284ecb25d5454692adf2f7548a5ca1c32023-11-24T07:31:59ZengMDPI AGAntioxidants2076-39212022-11-011111223810.3390/antiox11112238Quercetin Ameliorates Renal Injury and Pyroptosis in Lupus Nephritis through Inhibiting IL-33/ST2 Pathway In Vitro and In VivoHsin-Yuan Chen0Yi-Fen Chiang1Yong-Han Hong2Tzong-Ming Shieh3Tsui-Chin Huang4Mohamed Ali5Hsin-Yi Chang6Kai-Lee Wang7Shih-Min Hsia8School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, TaiwanSchool of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, TaiwanGraduate Programs of Nutrition Science, School of Life Science, National Taiwan Normal University, Taipei 106209, TaiwanSchool of Dentistry, College of Dentistry, China Medical University, Taichung 40402, TaiwanGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanClinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptGraduate Institute of Medical Science, National Defense Medical Center, Taipei 114, TaiwanDepartment of Nursing, Ching Kuo Institute of Management and Health, Keelung 20301, TaiwanSchool of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, TaiwanLupus nephritis (LN) is a common and serious symptom in patients with systemic lupus erythematosus (SLE). Tubular interstitial fibrosis is a common underlying mechanism in the development of lupus nephritis to end-stage renal failure (ESRD). Quercetin is widely proven to prevent tissue fibrosis. Therefore, the purpose of this study is to investigate the beneficial effects of quercetin on the inhibition of fibrosis and inflammation pathways in in vitro and in vivo lupus nephritis models. In the current study, MRL/lpr mice as animal models, and HK-2 human renal tubular epithelial cells were stimulated by interleukin-33 (IL-33) to mimic the cellular model of lupus nephritis. Immunohistochemical staining, immunoblotting assay, immunofluorescence staining, and quantitative real-time polymerase chain reaction assay were used. The in vivo results showed that quercetin improved the renal function and inhibited both fibrosis- and inflammation-related markers in MRL/lpr mice animal models. The in vitro results indicated that quercetin ameliorated the accumulation of fibrosis- and inflammation-related proteins in IL-33-induced HK-2 cells and improved renal cell pyroptosis via the IL33/ST2 pathway. Overall, quercetin can improve LN-related renal fibrosis and inflammation, which may offer an effective potential therapeutic strategy for lupus nephritis.https://www.mdpi.com/2076-3921/11/11/2238systemic lupus erythematosuslupus nephritisrenal fibrosisinflammationinterleukin-33quercetin |
| spellingShingle | Hsin-Yuan Chen Yi-Fen Chiang Yong-Han Hong Tzong-Ming Shieh Tsui-Chin Huang Mohamed Ali Hsin-Yi Chang Kai-Lee Wang Shih-Min Hsia Quercetin Ameliorates Renal Injury and Pyroptosis in Lupus Nephritis through Inhibiting IL-33/ST2 Pathway In Vitro and In Vivo Antioxidants systemic lupus erythematosus lupus nephritis renal fibrosis inflammation interleukin-33 quercetin |
| title | Quercetin Ameliorates Renal Injury and Pyroptosis in Lupus Nephritis through Inhibiting IL-33/ST2 Pathway In Vitro and In Vivo |
| title_full | Quercetin Ameliorates Renal Injury and Pyroptosis in Lupus Nephritis through Inhibiting IL-33/ST2 Pathway In Vitro and In Vivo |
| title_fullStr | Quercetin Ameliorates Renal Injury and Pyroptosis in Lupus Nephritis through Inhibiting IL-33/ST2 Pathway In Vitro and In Vivo |
| title_full_unstemmed | Quercetin Ameliorates Renal Injury and Pyroptosis in Lupus Nephritis through Inhibiting IL-33/ST2 Pathway In Vitro and In Vivo |
| title_short | Quercetin Ameliorates Renal Injury and Pyroptosis in Lupus Nephritis through Inhibiting IL-33/ST2 Pathway In Vitro and In Vivo |
| title_sort | quercetin ameliorates renal injury and pyroptosis in lupus nephritis through inhibiting il 33 st2 pathway in vitro and in vivo |
| topic | systemic lupus erythematosus lupus nephritis renal fibrosis inflammation interleukin-33 quercetin |
| url | https://www.mdpi.com/2076-3921/11/11/2238 |
| work_keys_str_mv | AT hsinyuanchen quercetinamelioratesrenalinjuryandpyroptosisinlupusnephritisthroughinhibitingil33st2pathwayinvitroandinvivo AT yifenchiang quercetinamelioratesrenalinjuryandpyroptosisinlupusnephritisthroughinhibitingil33st2pathwayinvitroandinvivo AT yonghanhong quercetinamelioratesrenalinjuryandpyroptosisinlupusnephritisthroughinhibitingil33st2pathwayinvitroandinvivo AT tzongmingshieh quercetinamelioratesrenalinjuryandpyroptosisinlupusnephritisthroughinhibitingil33st2pathwayinvitroandinvivo AT tsuichinhuang quercetinamelioratesrenalinjuryandpyroptosisinlupusnephritisthroughinhibitingil33st2pathwayinvitroandinvivo AT mohamedali quercetinamelioratesrenalinjuryandpyroptosisinlupusnephritisthroughinhibitingil33st2pathwayinvitroandinvivo AT hsinyichang quercetinamelioratesrenalinjuryandpyroptosisinlupusnephritisthroughinhibitingil33st2pathwayinvitroandinvivo AT kaileewang quercetinamelioratesrenalinjuryandpyroptosisinlupusnephritisthroughinhibitingil33st2pathwayinvitroandinvivo AT shihminhsia quercetinamelioratesrenalinjuryandpyroptosisinlupusnephritisthroughinhibitingil33st2pathwayinvitroandinvivo |