Wnt pathway regulates IL-34 level in lupus nephritis

Area of Science:

• Nephrology
• Immunology
• Cell Biology

Background:

• Interleukin-34 (IL-34) is implicated in autoimmune diseases.
• The Wnt signaling pathway plays a critical role in cellular processes.
• Dysregulation of these pathways may contribute to lupus nephritis (LN) pathogenesis.

Purpose of the Study:

• To investigate the Wnt pathway's regulation of IL-34 in LN.
• To explore the mechanistic link between Wnt signaling and IL-34 in LN.
• To assess the impact of Wnt pathway modulation on human mesangial cells (HMCs) in LN.

Main Methods:

• Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot to measure IL-34 expression in HMCs from LN patients.
• Treatment of HMCs with the Wnt pathway antagonist DKK1.
• Assessment of HMC viability using cell counting kit-8 (CCK-8) and colony formation assays.

Main Results:

• IL-34 mRNA and protein levels were significantly upregulated in HMCs from LN patients.
• Wnt pathway activation, indicated by β-catenin expression, was higher in LN HMCs and reduced by DKK1.
• DKK1 treatment downregulated IL-34 expression and enhanced HMC proliferation and colony formation in LN patients.

Conclusions:

• IL-34 is overexpressed in HMCs of LN patients.
• The Wnt pathway negatively regulates IL-34 expression in LN.
• Inhibiting the Wnt pathway enhances HMC viability in LN, suggesting a therapeutic target.