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

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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.

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Data Availability

Data supporting the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China, grant number (82173515, 82003454, 81872626).

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Authors and Affiliations

  1. Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China

    Lulu Tang, Dongdong Zhang, Yujing Zhang, Yangyang Peng, Mengxin Li, Hanlu Song, Hao Chen, Wenjie Li & Xing Li

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  1. Lulu Tang
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  2. Dongdong Zhang
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Contributions

Substantial contributions to the conception or design of the work: Lu-Lu Tang, Xing Li. Substantial contributions to the acquisition, analysis or interpretation of data for the work: Lu-Lu Tang, Xing Li and Dong-Dong Zhang. Drafting the work or revising it critically for important intellectual content: Lu-Lu Tang, Xing Li, Dong-Dong Zhang, Yu-Jing Zhang, Yang-Yang Peng, Meng-Xin Li, Han-Lu Song, Hao Chen and Wen-Jie Li. Final approval of the version to be published: Lu-Lu Tang, Xing Li, Dong-Dong Zhang, Yu-Jing Zhang, Yang-Yang Peng, Meng-Xin Li, Han-Lu Song, Hao Chen and Wen-Jie Li.

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Correspondence to Xing Li.

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All experiments involving animal subjects were performed in accordance with guidelines approved by the Animal Care and Use Committee of Zhengzhou University (ZZUGZR2018-035).

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Tang, L., Zhang, D., Zhang, Y. et al. Vitamin D3 alleviates lung fibrosis of type 2 diabetic rats via SIRT3 mediated suppression of pyroptosis. Apoptosis 28, 1618–1627 (2023). https://doi.org/10.1007/s10495-023-01878-6

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