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GGA (geranylgeranylacetone) ameliorates bleomycin-induced lung inflammation and pulmonary fibrosis by inhibiting apoptosis and oxidative stress

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Abstract

Background

Fibrosis is a response to ongoing cellular injury, disruption, and tissue remodeling, the pathogenesis of which is unknown, and is characterized by extracellular matrix deposition. The antifibrotic effect of Geranylgeranylacetone (GGA), as an inducer of Heat shock protein 70 (HSP70), in liver, kidney and pulmonary fibrosis has been supported by multiple preclinical evidence. However, despite advances in our understanding, the precise roles of HSP70 in fibrosis require further investigation. The purpose of this study was to investigate whether GGA could participate in the progression of pulmonary fibrosis in mice through apoptosis, oxidative stress and inflammation.

Methods and results

B-cell lymphoma-2(Bcl-2) and Bcl2-Associated X (Bax) are two proteins related to apoptosis. Anti-apoptotic factor Bcl-2 and pro-apoptotic factor Bax are often involved in the apoptotic process in the form of dimer. Immunofluorescence and Western blot results showed that bleomycin (BLM) and transforming growth factor-β (TGF-β) inhibited Bcl-2 expression and promoted Bax expression in vitro and in vivo, respectively. In contrast, GGA treatment reverses this change. Reactive oxygen species (ROS), Malondialdehyde (MDA) and superoxide dismutase (SOD) are markers of oxidative stress, which often reflect oxidative injury of cells. The detection of ROS, MDA and SOD expression showed that TGF-β and BLM treatment could significantly promote oxidative stress, while GGA treatment could alleviate oxidative stress damage. In addition, BLM significantly elevated Tumor necrosis factor-α(TNF-α), Interleukin1β (IL-1β) and Interleukin 6 (IL-6), while scutellarin reversed the above alterations except for that of GGA.

Results

Taken together, GGA suppressed apoptotic, oxidative stress and inflammation in BLM-induced pulmonary fibrosis.

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Data Availability

All data generated or analyzed during this study are included in this published article.

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Acknowledgements

This work was financed the Natural Science Foundation of Henan Province [grant numbers 222300420537]. In addition, we are thankful to Professor Fang Zhou for her advice and supporting this study.

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Authors and Affiliations

  1. Department of Occupational and Environmental Health Science, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China

    Rong Zhou, Chaomei Jin, Linlin Jiao, Siyu Zhang, Mei Tian, Jiamin Liu, Songtai Yang, Wu Yao & Fang Zhou

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Correspondence to Wu Yao or Fang Zhou.

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Zhou, R., Jin, C., Jiao, L. et al. GGA (geranylgeranylacetone) ameliorates bleomycin-induced lung inflammation and pulmonary fibrosis by inhibiting apoptosis and oxidative stress. Mol Biol Rep 50, 7215–7224 (2023). https://doi.org/10.1007/s11033-023-08590-3

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