p66shc exacerbates the progression of obstructive nephropathy through apoptosis, mitochondrial damage, and EMT

Background

Many factors contribute to hydronephrosis, ultimately resulting in renal fibrosis and even deterioration of renal function. This study investigated the pathogenic role of p66shc, a redox-regulatory protein, in hydronephrosis-induced renal injury.

Objective

This study focused on the mechanism of p66shc in renal fibrosis associated with obstructive nephropathy.

Methods

The expression of p66shc was found in kidney samples from pediatric hydronephrosis patients. A complete unilateral ureteral obstruction (CUUO) model was established in neonatal mice to recapitulate hydronephrotic progression. Cell proliferation, apoptosis, reactive oxygen species (ROS), mitochondrial damage, and degree of epithelial-mesenchymal transition (EMT) in renal tubular epithelial cells were studied following p66shc silencing and overexpression. We also investigated the therapeutic effects of silencing p66shc in vivo and carried out RNA sequencing after overexpressing p66shc in cells.

Results

p66shc inhibited renal tubular epithelial cell growth, exacerbated cell oxidative and mitochondrial damage, and promoted cell apoptosis and EMT. Silencing its expression in vivo could efficiently reduce renal fibrosis. Combined with RNA sequencing, we analyzed the potential molecular mechanisms of p66shc downstream.

Conclusion

p66shc enhances cell damage and the EMT process in obstructive nephropathy. Suppressing the expression of p66shc is one potential strategy for mitigating renal fibrotic progression.