Vitamin D3 alleviates lung fibrosis of type 2 diabetic rats via SIRT3 mediated suppression of pyroptosis.

Abstract

PURPOSE:

We aimed to evaluate whether pulmonary fibrosis occurs in type 2 diabetes rat models and whether VD3 can prevent it by inhibiting pyroptosis.

METHODS:

Sprague-Dawley rats were assigned to normal control (NC), diabetic model control (MC), low-dose VD3 (LVD), medium-dose VD3 (MVD), high-dose VD3 (HVD) and metformin positive control (PC) groups. Type 2 diabetes model was induced by a high-sugar, high-fat diet combined with STZ injection, and subsequently intervened with VD3 or metformin for 10 weeks. Blood glucose, body weight, food intake, water intake, urine volume, morphology, lung hydroxyproline level, immunohistochemistry, TUNEL staining, inflammatory cytokines secretion and related protein expression were analyzed.

RESULTS:

Diabetic rats exhibited significant impairments in fasting blood glucose, insulin resistance, body weight, food intake, water intake, and urine volume. While morphological parameters, diabetic rats exhibited severe lung fibrosis. Intriguingly, VD3 intervention reversed, at least in part, the diabetes-induced alterations. The expression of pyroptosis-related proteins was up-regulated in diabetic lungs whereas the changes were reversed by VD3. In the meanwhile, SIRT3 expression was down-regulated in diabetic lungs while VD3 up-regulated it.

CONCLUSION:

Fibrotic changes were observed in diabetic rat lung tissue and our study indicates that VD3 may effectively ameliorate diabetic pulmonary fibrosis via SIRT3-mediated suppression of pyroptosis.

• Authors: Lulu Tang, Dongdong Zhang, Yujing Zhang, Yangyang Peng, Mengxin Li, Hanlu Song, Hao Chen, Wenjie Li, Xing Li
• Journal: Apoptosis : an international journal on programmed cell death (Apoptosis) Vol. 28 Issue 11-12 Pg. 1618-1627 (12 2023) ISSN: 1573-675X [Electronic] Netherlands
• PMID: 37530936 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Cholecalciferol
• Sirtuin 3
• Blood Glucose
• Metformin

Topics

• Rats
• Animals
• Cholecalciferol (pharmacology)
• Pulmonary Fibrosis (drug therapy)
• Sirtuin 3 (adverse effects)
• Diabetes Mellitus, Type 2 (complications, drug therapy)
• Diabetes Mellitus, Experimental (metabolism)
• Rats, Sprague-Dawley
• Pyroptosis
• Blood Glucose
• Apoptosis
• Metformin (pharmacology, therapeutic use)
• Body Weight