Inhibition of WISE preserves renal allograft function

Area of Science:

• Nephrology
• Immunology
• Molecular Biology

Background:

• Wnt signaling activation is linked to interstitial fibrosis and tubular atrophy in renal transplants.
• The role of Wnt-modulator in surface ectoderm (WISE) in chronic kidney disease progression remains unclear.

Purpose of the Study:

• To investigate the contribution of WISE to renal dysfunction and fibrosis in a rat model of renal transplantation.
• To evaluate the therapeutic potential of targeting WISE in kidney allografts.

Main Methods:

• Assessed WISE mRNA expression in normal and transplanted rat kidneys.
• Administered a neutralizing antibody against WISE to rats post-transplantation.
• Evaluated graft function, proteinuria, inflammatory cell infiltration, histological injury, and gene expression.

Main Results:

• WISE mRNA was moderately to highly expressed in transplanted kidneys.
• Anti-WISE antibody treatment improved proteinuria and graft function.
• Treatment reduced macrophage and T cell infiltration, attenuated kidney injury, and decreased pro-fibrotic and immune response gene expression.
• Increased beta-catenin protein levels were observed in allografts following anti-WISE treatment.

Conclusions:

• WISE plays a significant role in promoting tubular atrophy and interstitial fibrosis in renal transplantation.
• Targeting WISE with neutralizing antibodies represents a potential therapeutic strategy to mitigate chronic kidney allograft dysfunction.