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Updated: Aug 29, 2025
Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Complement factor B inhibitor LNP023 improves lupus nephritis in MRL/lpr mice
Keng Chen1, Yiyao Deng2, Shunlai Shang3
1Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China; Haihe Laboratory of Cell Ecosystem, Tianjin 300450, China; Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou 510006, China.
LNP023 treatment significantly improved lupus nephritis (LN) in MRL/lpr mice by inhibiting the alternative complement pathway. This therapeutic effect involves regulating key targets like AKT, TNF-α, and STST3.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), often driven by alternative complement pathway activation.
- LNP023, a complement factor B (CFB) inhibitor, has shown promise in various renal diseases involving complement dysregulation.
- Understanding LNP023's efficacy in LN is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the therapeutic potential of LNP023 in a mouse model of lupus nephritis (MRL/lpr mice).
- To elucidate the mechanism by which LNP023 ameliorates LN, focusing on the alternative complement pathway.
- To identify core molecular targets of LNP023 in LN treatment.
Main Methods:
- MRL/lpr mice were treated with LNP023 or saline, alongside a normal control group.
- Evaluated lupus-like signs, renal pathology, function, immune complex deposition, and serum autoantibodies.
- Utilized network pharmacology to identify LNP023's core targets and validated their expression in patient samples and mouse models.
Main Results:
- LNP023 treatment reduced lupus signs, improved renal function, and decreased autoantibodies and immune deposits in MRL/lpr mice.
- Histopathological analysis revealed attenuated kidney damage, with reduced inflammation and crescent formation.
- Identified AKT, TNF-α, and STST3 as key targets regulated by LNP023, with altered expression in LN patients and treated mice.
Conclusions:
- LNP023 effectively improves lupus nephritis in MRL/lpr mice by inhibiting the alternative complement pathway via CFB binding.
- The therapeutic benefits of LNP023 in LN are associated with the modulation of AKT, TNF-α, and STST3 protein expression.
- LNP023 represents a potential therapeutic agent for lupus nephritis.
