Complement factor B inhibitor LNP023 improves lupus nephritis in MRL/lpr mice

作者：Keng Chen, Yiyao Deng, Shunlai Shang, Lifeng Tang, Qinggang Li, Xueyuan Bai, Xiangmei Chen · 发表于：Biomedicine & Pharmacotherapy · 年份：2022 · DOI：10.1016/j.biopha.2022.113433 · 被引用次数：31 · 研究领域：Complement system in diseases、Renal Diseases and Glomerulopathies、Systemic Lupus Erythematosus Research

BACKGROUND: Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE), and the abnormal activation of the alternative complement pathway is associated with the pathogenesis of LN. As an inhibitor of complement factor B (CFB) in the alternative pathway, LNP023 has been used in the treatment of a variety of renal diseases with abnormal complement system involvement, such as paroxysmal nocturnal hemoglobinuria, IgA nephropathy, and membranous nephropathy. The aim of our study was to explore whether LNP023 improved LN in MRL/lpr mice by inhibiting the activation of the alternative complement pathway. METHODS: The mice were divided into a normal control group (Normal group) (n = 6), MRL/lpr model group (n = 6), and LNP023 group (n = 6). The LNP023 group was administered LNP023 for 2 weeks by gavage; the MRL/lpr model group was administered saline for 2 weeks by gavage; and the Normal group was administered saline for 2 weeks by gavage. External signs, renal pathology, renal function, renal immune complex and complement deposition, serum anti-dsDNA, serum ANA concentration, and the expression of core complement factors in the alternative complement pathway were analyzed in the 3 groups of animals. The core targets of LNP023 in the treatment of LN were screened using network pharmacology. The pathogenicity of the core targets in LN was verified by analyzing the mRNA expression of the core targets in the peripheral blood mononuclear cells (PBMCs) of n...