posted on 2024-02-23, 20:14authored byQiong Wen, Cong Wang, Dongni Chen, Ning Luo, Jinjin Fan, Yi Zhou, Xueqing Yu, Wei Chen
This
study aimed to identify potential therapeutic targets
of artesunate
in an MRL/lpr lupus nephritis mouse model by quantitative proteomics.
We detected serum autoimmune markers and proteinuria in 40 female
mice that were divided into 4 groups (n = 10): normal
C57BL/6 control group; untreated MRL/lpr lupus; 9 mg/kg/day prednisone
positive control MRL/lpr lupus; and 15 mg/kg/day artesunate-treated
MRL/lpr lupus groups. Renal pathology in the untreated MRL/lpr lupus
and artesunate groups was examined by Periodic acid-Schiff (PAS) staining.
Artesunate treatment in lupus mice decreased serum autoantibody levels
and proteinuria while alleviating lupus nephritis pathology. Through
tandem mass tag-tandem mass spectrometry (TMT-MS/MS) analyses, differentially
expressed proteins were identified in the artesunate group, and subsequent
functional prediction suggested associations with antigen presentation,
apoptosis, and immune regulation. Data are available via ProteomeXchange
with the identifier PXD046815. Parallel reaction monitoring (PRM)
analysis of the top 19 selected proteins confirmed the TMT-MS/MS results.
Immunohistochemistry, immunofluorescence, and Western blotting of
an enriched protein from PRM analysis, cathepsin S, linked to antigen
presentation, highlighted its upregulation in the untreated MRL/lpr
lupus group and downregulation following artesunate treatment. This
study suggests that artesunate holds potential as a therapeutic agent
for lupus nephritis, with cathepsin S identified as a potential target.