Ameliorated lupus nephritis in MRL/lpr mice with nanoparticle-mediated shRNA therapy

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B870
Abstract ID: 5361

Presenting Author:
Wenhai Shao , Associate Professor at Univ. of Cincinnati Col. of Med.

Abstract:

Lupus nephritis (LN) is the most common and severe manifestation of systemic lupus erythematosus (SLE).  Its pathogenesis is complex and incomplete understood. Therapy approach are predominantly nonspecific immunosuppressive medications. MRL/lpr mice develop lupus nephritis that mostly assemble disease manifestation in lupus patients. WD repeats and FYVE domain-containing protein 1 (WDFY1) is an adaptor protein involving in inflammatory pathways. We found significantly enhanced WDFY1 expression in the kidney of MRL/lpr mice compared to the age/sex-matched MRL/MpJ mice. Kidney sections from LN patients also showed increased WDFY1 expression compared to kidney samples from healthy controls. Twelve-week MRL/lpr mice were treated with nanoparticle encapsuled WDFY1-shRNA for 5 weeks. Renal pathology, immune complex deposition, and complement activation were examined. MRL/lpr mice treated with nanoparticle encapsuled WDFY1-shRNA showed improved kidney function with significantly decreased proteinuria. Immunofluorescent staining of kidney sections revealed reduced immune cell infiltration and complement C3 deposition. Observations made here support the usefulness of WDFY1 for the treatment of lupus nephritis. Results may lead to more effective and safer molecule-specific approaches.