Tags

Type your tag names separated by a space and hit enter

Downregulation of HMGB1 is required for the protective role of Nrf2 in EMT-mediated PF.
J Cell Physiol. 2019 06; 234(6):8862-8872.JC

Abstract

Epithelial-mesenchymal transition (EMT) is considered to be the key event in the formation of pulmonary fibrosis (PF). High-mobility group box 1 (HMGB1) is a novel mediator of EMT. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical transcription factor for protecting against PF. However, it is unknown the relationship between Nrf2 and HMGB1 in EMT-mediated PF. Bleomycin (BLM)-induced PF in Nrf2-knockout (Nrf2-/-) and wild-type (WT) mice and transforming growth factor β1 (TGF-β1)-induced EMT in rat type II alveolar epithelial cell line (RLE-6TN) and human alveolar epithelial cell line (A549) were established to observe the relationship among Nrf2, HMGB1, and EMT by western blot and immunohistochemistry. BLM-induced EMT was more severe and the expression of HMGB1 was more increased in Nrf2 -/- mice compared with WT mice. In vitro, Nrf2 activation attenuated TGF-β1-induced EMT and ROS production accompanied by the downregulation of HMGB1. In contrast, silencing Nrf2 enhanced TGF-β1-induced EMT and ROS production along with increased the protein expression and the release of HMGB1. Moreover, HMGB1 activation aggravated TGF-β1-induced EMT and HMGB1 deficiency alleviated TGF-β1-induced EMT. Furthermore, HMGB1 silence attenuated the protective effect of Nrf2 on EMT. These findings suggest downregulation of HMGB1, which is required for the protective role of Nrf2 in EMT-mediated PF and provide an important therapeutic target for PF.

Authors+Show Affiliations

The Second Affiliated Hospital and School of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.The First Affiliated Hospital and School of Pharmacy, Anhui Medical University, Hefei, Anhui, China.The Second Affiliated Hospital and School of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.The First Affiliated Hospital and School of Pharmacy, Anhui Medical University, Hefei, Anhui, China.The First Affiliated Hospital and School of Pharmacy, Anhui Medical University, Hefei, Anhui, China.The First Affiliated Hospital and School of Pharmacy, Anhui Medical University, Hefei, Anhui, China.The First Affiliated Hospital and School of Pharmacy, Anhui Medical University, Hefei, Anhui, China.The Second Affiliated Hospital and School of Pharmacy, Dalian Medical University, Dalian, Liaoning, China. The First Affiliated Hospital and School of Pharmacy, Anhui Medical University, Hefei, Anhui, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30370641

Citation

Qu, Jiao, et al. "Downregulation of HMGB1 Is Required for the Protective Role of Nrf2 in EMT-mediated PF." Journal of Cellular Physiology, vol. 234, no. 6, 2019, pp. 8862-8872.
Qu J, Zhang Z, Zhang P, et al. Downregulation of HMGB1 is required for the protective role of Nrf2 in EMT-mediated PF. J Cell Physiol. 2019;234(6):8862-8872.
Qu, J., Zhang, Z., Zhang, P., Zheng, C., Zhou, W., Cui, W., Xu, L., & Gao, J. (2019). Downregulation of HMGB1 is required for the protective role of Nrf2 in EMT-mediated PF. Journal of Cellular Physiology, 234(6), 8862-8872. https://doi.org/10.1002/jcp.27548
Qu J, et al. Downregulation of HMGB1 Is Required for the Protective Role of Nrf2 in EMT-mediated PF. J Cell Physiol. 2019;234(6):8862-8872. PubMed PMID: 30370641.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Downregulation of HMGB1 is required for the protective role of Nrf2 in EMT-mediated PF. AU - Qu,Jiao, AU - Zhang,Zhihui, AU - Zhang,Panpan, AU - Zheng,Cheng, AU - Zhou,Wencheng, AU - Cui,Wenhui, AU - Xu,Liang, AU - Gao,Jian, Y1 - 2018/10/28/ PY - 2018/05/04/received PY - 2018/09/13/accepted PY - 2018/10/30/pubmed PY - 2020/4/18/medline PY - 2018/10/30/entrez KW - HMGB1 KW - Nrf2 KW - epithelial-mesenchymal transition KW - pulmonary fibrosis SP - 8862 EP - 8872 JF - Journal of cellular physiology JO - J Cell Physiol VL - 234 IS - 6 N2 - Epithelial-mesenchymal transition (EMT) is considered to be the key event in the formation of pulmonary fibrosis (PF). High-mobility group box 1 (HMGB1) is a novel mediator of EMT. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical transcription factor for protecting against PF. However, it is unknown the relationship between Nrf2 and HMGB1 in EMT-mediated PF. Bleomycin (BLM)-induced PF in Nrf2-knockout (Nrf2-/-) and wild-type (WT) mice and transforming growth factor β1 (TGF-β1)-induced EMT in rat type II alveolar epithelial cell line (RLE-6TN) and human alveolar epithelial cell line (A549) were established to observe the relationship among Nrf2, HMGB1, and EMT by western blot and immunohistochemistry. BLM-induced EMT was more severe and the expression of HMGB1 was more increased in Nrf2 -/- mice compared with WT mice. In vitro, Nrf2 activation attenuated TGF-β1-induced EMT and ROS production accompanied by the downregulation of HMGB1. In contrast, silencing Nrf2 enhanced TGF-β1-induced EMT and ROS production along with increased the protein expression and the release of HMGB1. Moreover, HMGB1 activation aggravated TGF-β1-induced EMT and HMGB1 deficiency alleviated TGF-β1-induced EMT. Furthermore, HMGB1 silence attenuated the protective effect of Nrf2 on EMT. These findings suggest downregulation of HMGB1, which is required for the protective role of Nrf2 in EMT-mediated PF and provide an important therapeutic target for PF. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/30370641/Downregulation_of_HMGB1_is_required_for_the_protective_role_of_Nrf2_in_EMT_mediated_PF_ L2 - https://doi.org/10.1002/jcp.27548 DB - PRIME DP - Unbound Medicine ER -