Investigation on the relationship between renal NONO expression, fibrosis and prognosis in diabetic nephropathy

TL;DR

This study finds that higher NONO protein levels in kidney tissues are linked to worse outcomes in diabetic nephropathy, possibly by increasing fibrosis and MMP-9 activity.

Contribution

The study identifies a novel role for NONO in diabetic nephropathy fibrosis and prognosis through its correlation with MMP-9 and clinical indicators.

Findings

NONO expression is elevated in diabetic nephropathy and correlates with fibrosis markers like MMP-9 and collagen.

High NONO levels are associated with poorer kidney survival rates in diabetic nephropathy patients.

NONO expression increases with disease progression from early to late stages of diabetic nephropathy.

Abstract

Renal interstitial fibrosis (RIF) is an important manifestation of Diabetic nephropathy (DN) progression. Non-POU domain containing octamer-binding protein (NONO) is crucial in fibrosis in cardiovascular diseases, but its role in DN fibrosis remains unclear. This study explores the expression of NONO in DN and its correlation with Matrix Metalloproteinase-9 (MMP-9, as an important regulator of fibrosis), renal fibrosis, and prognosis.

Forty patients with type 2 diabetes mellitus (T2DM) with pathologically confirmed DN were included, divided into early DN group (n=20) and late DN group (n=20). 6 normal renal tissue as control group. HE, Masson staining, immunohistochemical staining and Immunofluorescence double staining were performed. The correlation between NONO expression levels and MMP-9 as well as clinical pathological data was analyzed. Cox regression analysis and Kaplan-Meier survival curves were used to evaluate the relationship between renal tissue NONO expression levels and DN prognosis.

Compared with control group, NONO expression levels in renal tissues of DN patient were increased, and the late DN group was higher than the early DN group (P<0.05). NONO and MMP-9 expression were positively correlated with multiple clinical and Fibrosis-related pathological indicators, and NONO expression was positively correlated with MMP-9(P<0.05). Patients with high renal NONO expression had lower kidney progression-free survival rates.

NONO expression levels correlate positively with MMP-9, collagen and renal damage indicators in renal tissues of DN patients. High NONO expression is linked to poor renal prognosis in DN. NONO may contribute to renal tissue fibrosis in DN by regulating MMP-9 levels.

We investigated the expression of the NONO protein across various stages of diabetic nephropathy and its association with clinical prognosis through renal tissue staining and statistical analysis, indicating that NONO may play a significant role in the pathogenesis and progression of diabetic nephropathy.

Flowchart and data visualization depicting research methodology and results. The top section outlines study groups: control, early Diabetic Nephropathy (DN), and late DN, involving renal biopsy and statistical analysis. Below, images show immunohistochemistry (IHC) and immunofluorescence (IF) for NONO protein in glomeruli and renal tubules across groups. Statistical analysis includes box plots displaying NONO expression intensity and fluorescence intensity, and graphs analyzing specificity, sensitivity, and survival probability.

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