Neuropilin-1 as a Key Molecule for Renal Recovery in Lupus Nephritis: Insights from an NZB/W F1 Mouse Model

Int J Mol Sci. 2024 Oct 22;25(21):11364. doi: 10.3390/ijms252111364.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organs, with lupus nephritis (LN) occurring in 40-50% of SLE patients. Despite advances in diagnosis and treatment, LN remains a major cause of morbidity and mortality, with 10-20% of patients progressing to end-stage renal disease (ESRD). While knowledge of LN's pathogenesis has improved, mechanisms of renal recovery are still largely unexplored. Neuropilin-1 (NRP-1), a transmembrane receptor expressed in renal tissue, has emerged as a promising biomarker for assessing renal recovery in LN. This study evaluates and correlates longitudinal levels of NRP-1 with kidney histology using an NZB/W F1 mouse model of LN. A total of 30 mice were used, with 15 receiving intravenous cyclophosphamide (CYC) and 15 being untreated. NRP-1 levels were measured in urine and serum, and kidney samples were taken from a subgroup of mice for histological evaluation. The results demonstrated a progressive increase in renal and urinary NRP-1 expression, particularly notable at weeks 26 and 32. Urinary NRP-1 levels above 34.40 ng/mL were strong predictors of favorable renal response, showing 100% sensitivity and 88% specificity. These findings indicate a robust correlation between urinary NRP-1 levels and renal histological recovery, underscoring the potential of NRP-1 as a valuable biomarker for assessing renal response in LN. This study demonstrates that renal production of NRP-1 is linked to histological recovery and establishes a foundation for future research into the role of NRP-1 in lupus kidney recovery.

Keywords: biomarker; lupus nephritis (LN); neuropilin-1 (NRP-1); renal recovery; systemic lupus erythematosus (SLE).

MeSH terms

  • Animals
  • Biomarkers*
  • Cyclophosphamide* / therapeutic use
  • Disease Models, Animal*
  • Female
  • Kidney* / metabolism
  • Kidney* / pathology
  • Lupus Nephritis* / metabolism
  • Lupus Nephritis* / pathology
  • Mice
  • Mice, Inbred NZB
  • Neuropilin-1* / metabolism

Substances

  • Neuropilin-1
  • Biomarkers
  • Cyclophosphamide

Grants and funding

This research received no external funding.