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Updated: Oct 23, 2025
Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Microarray-based analysis of renal complement components reveals a therapeutic target for lupus nephritis
Tao Liu1, Mingyue Yang2, Ying Xia2
1Department of Rheumatology and Immunology, The First Hospital of Jilin University, Changchun, 130021, China.
Background:
Screening abnormal pathways and complement components in the kidneys of patients with lupus nephritis (LN) and NZB/W mice may help to identify complement-related therapeutic targets for LN.
Methods:
KEGG and GO enrichment assays were used to analyze kidney microarray data of LN patients and NZB/W mice. Immunohistochemistry and immunofluorescence assays were used to measure renal expression of complement-related proteins and TGFβ1. Cytokines were measured using RT-qPCR and ELISA.
Results:
We screened the renal pathogenic pathways present in LN patients and NZB/W mice and selected the complement activation pathway for further study. The results indicated greater renal expression of C1qa, C1qb, C3, C3aR1, and C5aR1 at the mRNA and protein levels. C3 appeared to be a key factor in LN and the renal signaling downstream of C1 was inhibited. There were significant correlations between the expression of TGFβ1 and C3. Analysis of primary cell cultures indicated that TGFβ1 promoted the expression of C3 and that a TGFβ1 antagonist decreased the levels of C3 and C3aR. TGFβ1 inhibition significantly inhibited the deposition of complement-related factors in the kidneys of NZB/W mice.
Conclusions:
At the onset of LN, there are significant increases in the renal levels of C3 and other complement pathway-related factors in patients with LN and NZB/W mice. C3 may lead to albuminuria and participate in the pathogenesis of LN. TGFβ1 promotes C3 synthesis, and TGFβ1 inhibition may block the progression of LN by inhibiting the synthesis of C3 and other complement components.
Insights
Complement component C3 and TGFβ1 are key factors in lupus nephritis (LN) pathogenesis. Inhibiting TGFβ1 may block LN progression by reducing C3 synthesis and complement activation in the kidneys.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- Lupus nephritis (LN) involves abnormal kidney pathways and complement system activation.
- Identifying complement-related therapeutic targets is crucial for LN treatment.
Purpose of the Study:
- To screen abnormal pathways and complement components in LN kidneys.
- To investigate the role of complement activation and TGFβ1 in LN pathogenesis.
Main Methods:
- KEGG and GO enrichment assays on kidney microarray data from LN patients and NZB/W mice.
- Immunohistochemistry, immunofluorescence, RT-qPCR, and ELISA to measure renal expression of complement proteins and cytokines.
- Primary cell culture and TGFβ1 antagonist treatment to study TGFβ1-C3 interactions.
Main Results:
- Complement activation pathway identified as a key pathogenic pathway in LN.
- Increased renal expression of complement factors (C1qa, C1qb, C3, C3aR1, C5aR1) at mRNA and protein levels.
- Significant correlation between TGFβ1 and C3 expression; TGFβ1 promotes C3 synthesis, and its inhibition reduces C3 levels and complement deposition.
Conclusions:
- Elevated C3 and complement factors are present in LN kidneys at disease onset.
- C3 may contribute to albuminuria and LN pathogenesis.
- TGFβ1 inhibition offers a potential therapeutic strategy for LN by blocking C3 synthesis and complement component deposition.
