Quercetin Ameliorates Renal Injury and Pyroptosis in Lupus Nephritis through Inhibiting IL-33/ST2 Pathway In Vitro and In Vivo

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

doi:10.3390/antiox11112238

Quercetin Ameliorates Renal Injury and Pyroptosis in Lupus Nephritis through Inhibiting IL-33/ST2 Pathway In Vitro and In Vivo

Antioxidants (Basel). 2022 Nov 13;11(11):2238. doi: 10.3390/antiox11112238.

Authors

Hsin-Yuan Chen¹, Yi-Fen Chiang¹, Yong-Han Hong², Tzong-Ming Shieh³, Tsui-Chin Huang⁴, Mohamed Ali⁵, Hsin-Yi Chang⁶, Kai-Lee Wang⁷, Shih-Min Hsia^{1

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Affiliations

¹ School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, Taiwan.
² Graduate Programs of Nutrition Science, School of Life Science, National Taiwan Normal University, Taipei 106209, Taiwan.
³ School of Dentistry, College of Dentistry, China Medical University, Taichung 40402, Taiwan.
⁴ Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
⁵ Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
⁶ Graduate Institute of Medical Science, National Defense Medical Center, Taipei 114, Taiwan.
⁷ Department of Nursing, Ching Kuo Institute of Management and Health, Keelung 20301, Taiwan.
⁸ School of Food and Safety, Taipei Medical University, Taipei 110301, Taiwan.
⁹ Nutrition Research Center, Taipei Medical University Hospital, Taipei 110301, Taiwan.
¹⁰ Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.
¹¹ TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei 110301, Taiwan.

Abstract

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.

Keywords: inflammation; interleukin-33; lupus nephritis; quercetin; renal fibrosis; systemic lupus erythematosus.

Grants and funding

This study was supported by the grants MOST108-2320-B-214-001, MOST109-2314-B-038-059, MOST109-2628-B-038-015, MOST109-2320-B-254-001, MOST109-2314-B-214-004, MOST110-2314-B-038-158, and MOST110-2628-B-038-018 from the Ministry of Science and Technology, Taiwan. NSTC111-2811-B-038-022 and 111-2628-B-038-019 from the National of Science and Technology Council, Taiwan.