Microarray-Based Analysis of the Complements in Kidney Reveals a Therapeutic Target in Lupus Nephritis

Abstract Background: To screen abnormal pathways and complement components in the kidney of lupus nephritis (LN), and determine a local C3 related therapeutic target in LN.Methods: KEGG and GO enrichment assay were used to analyze the 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 local pathogenic pathways shared by LN patients and NZB/W mice in the kidney and selected the complement activation pathway for further study. We found greater expression of C1QA, C1QB, C3，C3AR1 and C5AR1 at the mRNA and protein levels. C3 is a key factor of the disease and the downstream of C1 is inhibited in the kidney. There were significant correlations between the expression of TGFβ1 and C3 in LN. In addition, our analysis of the primary cell-cultures indicated that TGFβ1 promoted the expression of C3 and that a TGFβ1 antagonist decreased the levels of C3 and C3AR in LN. TGFβ1 inhibition significantly inhibited the deposition of complement-related factors in the kidneys of NZB/W mice.Conclusions: At the onset of LN, there was significant renal up-regulation of C3 and other complement pathway-related factors in the kidneys of human 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.