Granzyme B promotes bleomycin-induced pulmonary fibrosis by activating TGF-β1/Smad3 pathway

doi:10.3877/cma.j.issn.1674-6902.2023.05.005

Abstract

Abstract:

Objective

To explore the role of granzyme B in bleomycin-induced pulmonary fibrosis in rats.

Methods

21 SD rats were randomly divided into three groups: control group, model group and intervention group, with 7 rats in each group. The model group and the intervention group were injected with bleomycin (5 mg/kg) through the trachea to induce pulmonary fibrosis. The intervention group was injected with granzyme B inhibitor through caudal vein 1 hour before modeling, on day 7, 14 and 21, and the other two groups were injected with equal volume of normal saline. The remaining operations were the same. After 28 days, the rats were killed and the lungs were removed. The protein expressions of granzyme B, collagen I, TGF-β1 and Smad3 were detected by immunofluorescence and Western blot, and the pulmonary fibrosis was detected by Masson staining.

Results

Compared with the control group, collagen I expression, collagen deposition and pulmonary fibrosis were up-regulated in the model group. Compared with model group, collagen I expression was down-regulated, collagen deposition was reduced and pulmonary fibrosis was alleviated in the intervention group. The protein expressions of TGF-β1 and Smad3 in lung tissue of model group were increased compared with that of control group, while the protein expressions of TGF-β1 and Smad3 in intervention group were decreased compared with that of model group.

Conclusion

Granzyme B can promote bleomycin-induced pulmonary fibrosis in rats, and the mechanism may be related to the activation of TGF-β1/Smad3 signaling pathway.

Key words: Pulmonary fibrosis, Granzyme B, TGF-β1, Smad3

Xiangjun Chen, Xing Gu, Zaiqiang Wang, Guanghui Wang, Li Wang, Fang Wan, Faguang Jin, Ruixuan Wang. Granzyme B promotes bleomycin-induced pulmonary fibrosis by activating TGF-β1/Smad3 pathway[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2023, 16(05): 630-634.

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References 30

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