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Updated: Dec 29, 2025
Induction of Mouse Lung Injury by Endotracheal Injection of Bleomycin
Published on: April 30, 2019
Blocking TG2 attenuates bleomycin-induced pulmonary fibrosis in mice through inhibiting EMT
Kai Wang1, Cuihua Zu1, Yan Zhang1
1Department of Anesthesiology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China.
Background:
Epithelial-mesenchymal transformation (EMT) is a central mechanism for the occurrence and development of pulmonary fibrosis. Therefore, to identify the key target molecules regulating the EMT process is considered as an important direction for the prevention and treatment of pulmonary fibrosis. Transglutaminase 2 (TG2) has been recently found to play an important role in the regulation of inflammation and the generation of extracellular matrix. Here, our study focuses on the roles of TG2 in pulmonary fibrosis and EMT.
Methods:
at first, the expression of TG2 and the EMT-related markers like E-cadherin, Vimentin, and α-SMA were detected with Western Blotting, immunohistochemistry and other methods in the mice with pulmonary fibrosis induced by bleomycin. Further, MLE 12 cells were used to study the effects on EMT of the inhibition of TG2 in vitro. Finally, GK921, an inhibitor against TG2, was used to show its function in both prevention and treatment of pulmonary fibrosis induced by bleomycin in mice.
Results:
bleomycin succeeded to induce pulmonary fibrosis in mice, with increased TG2 expression, EMT and Akt activation. Knock-down of TG2 by siRNA technique in MLE 12 cell (a mouse alveolar epithelial cell line) and GK921 (an inhibitor of TG2) all inhibited the EMT process, however SC79, an activator of Akt rescued above inhibition. Finally, GK921 alleviated pulmonary fibrosis in mice induced by bleomycin.
Conclusion:
Blocking TG2 reduces bleomycin-induced pulmonary fibrosis in mice via inhibiting EMT.
Insights
Blocking transglutaminase 2 (TG2) inhibits pulmonary fibrosis by preventing epithelial-mesenchymal transformation (EMT). This study highlights TG2 as a therapeutic target for treating lung fibrosis.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Biochemistry
Background:
- Epithelial-mesenchymal transformation (EMT) is crucial in pulmonary fibrosis development.
- Identifying key regulators of EMT is vital for treating pulmonary fibrosis.
- Transglutaminase 2 (TG2) is implicated in inflammation and extracellular matrix generation.
Purpose of the Study:
- To investigate the role of TG2 in pulmonary fibrosis and EMT.
- To evaluate TG2 as a potential therapeutic target for pulmonary fibrosis.
Main Methods:
- Assessed TG2 and EMT marker expression in bleomycin-induced pulmonary fibrosis mouse models.
- Utilized MLE 12 cells to study TG2 inhibition effects on EMT in vitro.
- Administered GK921, a TG2 inhibitor, to assess its preventive and therapeutic potential in mice.
Main Results:
- Bleomycin induced pulmonary fibrosis, increasing TG2 expression, EMT, and Akt activation.
- TG2 knockdown and GK921 treatment inhibited EMT in MLE 12 cells; Akt activation reversed this.
- GK921 treatment alleviated bleomycin-induced pulmonary fibrosis in mice.
Conclusions:
- Inhibition of TG2 reduces pulmonary fibrosis in mice.
- Blocking TG2 mitigates pulmonary fibrosis by inhibiting EMT.
- TG2 is a promising therapeutic target for pulmonary fibrosis.
