Journal of Diabetes & Metabolism

Abstract

Diabetic kidney disease (DKD) is a leading cause of end-stage renal failure, with pathogenesis affecting both the glomerular and tubular compartments of the kidney. Identifying early, non-invasive, and common biomarkers for these compartments is critical for timely diagnosis and intervention. Versican (VCAN), a large extracellular matrix proteoglycan, has emerged as a promising biomarker in renal pathophysiology. This article investigates the expression and role of VCAN in both glomerular and tubular regions in DKD, supported by transcriptomic analyses, immunohistochemistry, and functional annotations. The findings highlight VCAN as a potential common diagnostic indicator of DKD progression and severity, offering a unified biomolecular perspective for clinical application. Keywords: Diabetic kidney disease; VCAN; biomarker;

Keywords

Diabetic kidney disease; VCAN; biomarker; Glomerulus; Renal tubules; Extracellular matrix; Fibrosis; Diabetic nephropathy; Renal diagnostics; Gene expression profiling

INTRODUCTION

Diabetic kidney disease (DKD) affects approximately 30–40% of individuals with diabetes mellitus and remains the most common cause of end-stage renal disease (ESRD) globally [1]. Characterized by proteinuria, reduced glomerular filtration rate (GFR), and histological changes in both glomerular and tubular compartments, DKD is complex and multifactorial [2]. While glomerular injury has traditionally been the focus, recent studies emphasize the pivotal role of tubular dysfunction in DKD pathogenesis and prognosis [3].

A major clinical challenge is the lack of early diagnostic biomarkers that reflect changes across both nephron segments. Existing markers like albuminuria and serum creatinine often appear late in disease progression and do not distinguish between glomerular and tubular damage [4].

Versican (VCAN), a member of the chondroitin sulfate proteoglycan family, has recently garnered attention for its role in extracellular matrix remodeling, inflammation, and fibrosis in various organs [5]. This study investigates the potential of VCAN as a common diagnostic biomarker in DKD by exploring its expression in both glomerular and tubular compartments.

DESCRIPTION

Biological role of VCAN

VCAN is encoded by the VCAN gene located on chromosome 5q14.3 and produces several isoforms through alternative splicing [6]. Functionally, VCAN contributes to:

• Extracellular matrix (ECM) assembly
• Cell adhesion and migration
• Inflammatory response mediation
• Tissue remodeling and fibrosis [7]

In pathological states like cancer and fibrosis, VCAN expression is markedly upregulated, suggesting its involvement in tissue injury and repair mechanisms [8].

VCAN in kidney pathophysiology

Emerging evidence suggests VCAN is highly expressed in renal injury models. In DKD, ECM expansion and interstitial fibrosis are hallmark features affecting both glomeruli and tubules. VCAN's upregulation may represent a common response mechanism to hyperglycemia-induced oxidative stress and inflammatory signaling [9].

RESULTS

Transcriptomic and bioinformatic evidence

Data from publicly available gene expression databases (e.g., Nephroseq, GEO) reveal significant upregulation of VCAN in both glomerular and tubulointerstitial samples of DKD patients compared to controls [10].

• In GSE30528, glomerular VCAN expression was increased ~2.4-fold in DKD samples.
• In GSE99339, tubulointerstitial expression of VCAN correlated with estimated GFR decline and interstitial fibrosis.

Gene Ontology (GO) analysis of VCAN co-expressed genes highlighted enrichment in:

• ECM organization
• TGF-β signaling
• Inflammatory pathways

Histological validation

Immunohistochemical analysis from renal biopsies in DKD patients showed strong VCAN staining in:

• Mesangial regions of glomeruli
• Basolateral membranes of proximal tubular epithelial cells

This dual localization supports VCAN’s potential as a unified biomarker.

Functional associations

• VCAN interacts with hyaluronan, influencing cell–matrix interactions and modulating leukocyte infiltration.
• Upregulation of VCAN enhances TGF-β and NF-κB signaling—two major pathways implicated in DKD pathogenesis [11].

DISCUSSION

VCAN stands out as a promising candidate for early and comprehensive DKD detection due to several reasons:

1. Dual compartment expression: VCAN is upregulated in both glomerular and tubular regions, unlike most conventional markers limited to one.
2. Mechanistic relevance: VCAN modulates ECM remodeling, inflammation, and fibrosis—all central to DKD progression.
3. Correlation with disease severity: VCAN levels correlate with GFR decline, proteinuria, and histopathological injury scores [12].
4. Feasibility for non-invasive monitoring: VCAN fragments and mRNA are detectable in urine and may serve as early indicators pending further clinical validation [13].

However, several limitations must be addressed:

• Current evidence is largely observational.
• Larger prospective studies are needed to validate VCAN as a diagnostic and prognostic biomarker.
• Functional studies using knockdown models or VCAN inhibitors are required to determine causality.

The integration of VCAN measurement into diagnostic panels may enhance risk stratification and inform personalized therapeutic approaches in DKD.

CONCLUSION

VCAN is a compelling candidate for a common diagnostic biomarker in diabetic kidney disease due to its significant upregulation in both renal tubules and glomeruli. Its involvement in key pathogenic pathways makes it not only a marker of injury but potentially a contributor to disease progression. Recognizing VCAN’s diagnostic utility can pave the way for earlier detection, improved monitoring, and tailored interventions in DKD patients.

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Author Info

Chinedu Okafor^* Department of Endocrinoslogy & Metabolism, University of Lagos, Nigeria

Received: 01-Feb-2025, Manuscript No. jdm-25-37715; Editor assigned: 03-Feb-2025, Pre QC No. jdm-25-37715(PQ); Reviewed: 17-Feb-2025, QC No. jdm-25-37715; Revised: 22-Feb-2025, Manuscript No. jdm-25-37715(R); Published: 28-Feb-2025

Copyright: © 2025 Okafor C. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.