Complement 1q protects MRL/lpr mice against lupus nephritis via inhibiting the nuclear factor-κB pathway

Sun,Juanjuan; Guo,Shuxia; Niu,Fukun; Liu,Defeng; Zhuang,Yan

doi:10.3892/mmr.2020.11588

Complement 1q protects MRL/lpr mice against lupus nephritis via inhibiting the nuclear factor-κB pathway

Authors:
- Juanjuan Sun
- Shuxia Guo
- Fukun Niu
- Defeng Liu
- Yan Zhuang
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Affiliations: Department of Nephrology, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China
Published online on: October 14, 2020 https://doi.org/10.3892/mmr.2020.11588
Pages: 5436-5443

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Abstract

Lupus nephritis (LN) is a kidney disorder that is a critical cause of mortality in patients with systemic lupus erythematosus. The present study aimed to explore the protective role of complement component 1q (C1q) on LN and the underlying mechanism involving the nuclear factor (NF)‑κB singling pathway. MRL/lpr mice served as the LN mouse model, and pcDNA‑C1q was injected into LN mice to determine the role of C1q. C1q mRNA expression was detected using reverse transcription‑quantitative PCR. Urine protein and blood urea nitrogen (BUN) levels were measured, and the histological damage index was determined using H&E staining. ELISA was used to measure the levels of tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑1β, IL‑6, anti‑C1q and anti‑double stranded DNA (dsDNA). CD68‑ and Ki67‑positivity were detected using immunofluorescence, and NF‑κB‑related protein expression was examined using western blotting. C1q mRNA expression was downregulated in renal tissues of LN mice. Overexpression of C1q decreased urine protein, BUN levels and the histological damage index in LN mice. The levels of TNF‑α, IL‑1β, IL‑6, anti‑C1q and anti‑dsDNA in renal tissues of LN mice were also reduced after pcDNA‑C1q treatment. Additionally, overexpression of C1q decreased the CD68‑ and Ki67‑positivity in glomeruli and attenuated the expression of NF‑κB‑related proteins. Phorbol 12‑myristate 13‑acetate, an NF‑κB pathway activator, reversed the inhibitory effect of C1q on inflammation, macrophage infiltration and mesangial cell (MC) proliferation in renal tissues of LN mice. Thus, it was demonstrated that C1q ameliorated inflammation and macrophage infiltration and decreased MC proliferation in renal tissues of LN mice by inhibiting the NF-κB pathway.

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