Related Experiment Video For Glomerular injury
Updated: Feb 27, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Vitamin C deficiency exacerbates diabetic glomerular injury through activation of transforming growth factor-β
Xing Ji1, Xinhua Hu1, Chaochun Zou2
1Department of Pharmacology, Zhejiang University Medical School, Hangzhou 310058, China.
Background:
The hyperglycemia and hyperoxidation that characterize diabetes lead to reduced vitamin C (VC) in diabetic humans and experimentally diabetic animals. Herein, we access the effects of VC deficiency on the diabetic kidney injury and explore the underlying mechanism.
Methods:
l-gulonolactone oxidase conventional knockout (Gulo-/-) mice genetically unable to synthesize VC were subjected to streptozotocin-induced diabetic kidney injury and the role of VC deficiency was evaluated by biochemical and histological approaches. Rat mesangial cells were cultured to investigate the underlying mechanism.
Results:
Functionally, VC deficiency aggravates the streptozotocin-induced renal insufficiency, exhibiting the increased urine albumin, water intake, and urine volume in Gulo-/- mice. Morphologically, VC deficiency exacerbates the streptozotocin-induced kidney injury, exhibiting the increased glomerular expansion, deposition of Periodic Acid-Schiff- and Masson-positive materials, and expression of α-smooth muscle actin, fibronectin and type 4 collagen in glomeruli of Gulo-/- mice. Mechanistically, VC activates protein kinase B (Akt) to destabilize Ski and thereby induce the expression of Smad7, resulting in suppression of TGF-β/Smad signaling and extracellular matrix deposition in mesangial cells.
Conclusions:
VC is essential for the renal function maintenance in diabetes.
General Significance:
Compensation for the loss of VC could be an effective remedy for diabetic kidney injury.
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