Comparative Proteomics Analysis of Mouse Habu Nephritis Models with and without Unilateral Nephrectomy.

BACKGROUND/AIMS: Individuals possessing a single kidney are at greater risk of renal injury upon exposure to harmful stimuli. This study aimed to explore the pathogenesis of renal injury in glomerulonephritis with versus without unilateral nephrectomy (UNX).

METHODS: Histological analysis and label-free quantitative proteomics were performed on two models-the Habu snake venom-induced glomerulonephritis model with versus without UNX (HabuU and Habu models, respectively). The role of villin 1, a differentially expressed protein (DEP) in mouse mesangial cells, was investigated.

RESULTS: Persistent mesangiolysis and focal hypercellularity together with reduced activation of cell proliferation in the HabuU model induced more serious renal injury compared with that in the Habu model. The DEPs between the two models were identified by label-free liquid chromatography-mass spectrometry. The KEGG pathway results indicated that regulation of actin cytoskeleton and focal adhesion were specifically enriched in the HabuU model. The cytoskeleton regulation protein villin 1 was downregulated in the HabuU model, but unchanged in the Habu model. Knockdown of villin 1 promoted apoptosis and inhibited the proliferation of mouse mesangial cells, suggesting villin 1 to be involved in qlomerular lesion self-repair insufficiency.

CONCLUSION: By assessing the proteomic profiles of the two models, this study identified several important differences, particularly villin 1 expression, in regulatory mechanisms between the two models. Our findings provide novel insight into the mechanism of serious renal injury in glomerulonephritis with UNX.