| First Author | Ji X | Year | 2017 |
| Journal | Biochim Biophys Acta Gen Subj | Volume | 1861 |
| Issue | 9 | Pages | 2186-2195 |
| PubMed ID | 28652077 | Mgi Jnum | J:269897 |
| Mgi Id | MGI:6104546 | Doi | 10.1016/j.bbagen.2017.06.018 |
| Citation | Ji X, et al. (2017) Vitamin C deficiency exacerbates diabetic glomerular injury through activation of transforming growth factor-beta signaling. Biochim Biophys Acta 1861(9):2186-2195 |
| abstractText | 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 alpha-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-beta/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. |
