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Angptl2 deficiency attenuates paraquat (PQ)-induced lung injury in mice by altering inflammation, oxidative stress and fibrosis through NF-κB pathway.
Biochem Biophys Res Commun. 2018 09 03; 503(1):94-101.BB

Abstract

Paraquat (PQ) is one of the most extensively used herbicides, possessing high toxicity for humans and animals. The lung is the main target organ by the poisoning of PQ resulting in acute lung injury. Nonetheless, molecular mechanisms underlying PQ-induced lung injury remain unclear. Here, we ask if angiopoietin-like protein 2 (Angptl2), a pro-inflammatory protein, contributes to inflammation that accelerates acute lung injury. The results indicated that abundant Angptl2 expression was observed in lung tissues of PQ-treated mice. Histological analysis revealed that PQ-induced histological changes were alleviated by Angptl2 knockout (Angptl2-/-). Angptl2-/- in PQ-treated mice attenuated acute lung injury progression by reducing the number of total cells, total leukocytes, neutrophils and macrophages in bronchoalveolar lavage fluid (BALF) and reducing inflammatory response through the inactivation of nuclear factor kappa B (NF-κB) pathway. Angptl2-/- reduced oxidative stress in PQ-treated mice, as evidenced by the enhanced superoxide dismutase (SOD) activity and reduced malondialdehyde (MDA) levels in serum or lung tissue samples, which was accompanied with increased expressions of nuclear respiratory factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1). PQ-induced fibrosis was also improved in Angptl2-/- mice by decreasing pulmonary transforming growth factor (TGF)-β1 expressions. In vitro, we found that Angptl2 knockdown-suppressed inflammation, oxidative stress and fibrosis was restored by increasing NF-κB activation in PQ-incubated A549 cells; however, the results above were significantly reversed by inactivating NF-κB using its inhibitor, Bay 11-7085 or LY2409881. Therefore, Angptl2 could provide therapeutic effects on PQ-induced acute lung injury through inhibiting inflammation, oxidative stress and fibrosis by regulating NF-κB pathway.

Authors+Show Affiliations

Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, Nangang District, Harbin, 150001, China.Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, Nangang District, Harbin, 150001, China; Department of General Surgery, Xinxiang Medical University, No. 601, New Yan Road, Xinxiang 453000, China.Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, Nangang District, Harbin, 150001, China.Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, Nangang District, Harbin, 150001, China.Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, Nangang District, Harbin, 150001, China.Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, Nangang District, Harbin, 150001, China.Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, Nangang District, Harbin, 150001, China.Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, No. 23, YouZheng Street, Nangang District, Harbin, 150001, China. Electronic address: zhaomingyanzz@qq.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29852175

Citation

Yang, Wei, et al. "Angptl2 Deficiency Attenuates Paraquat (PQ)-induced Lung Injury in Mice By Altering Inflammation, Oxidative Stress and Fibrosis Through NF-κB Pathway." Biochemical and Biophysical Research Communications, vol. 503, no. 1, 2018, pp. 94-101.
Yang W, Liu W, Yu W, et al. Angptl2 deficiency attenuates paraquat (PQ)-induced lung injury in mice by altering inflammation, oxidative stress and fibrosis through NF-κB pathway. Biochem Biophys Res Commun. 2018;503(1):94-101.
Yang, W., Liu, W., Yu, W., Fei, D., Meng, X., Yang, S., Meng, S., & Zhao, M. (2018). Angptl2 deficiency attenuates paraquat (PQ)-induced lung injury in mice by altering inflammation, oxidative stress and fibrosis through NF-κB pathway. Biochemical and Biophysical Research Communications, 503(1), 94-101. https://doi.org/10.1016/j.bbrc.2018.05.186
Yang W, et al. Angptl2 Deficiency Attenuates Paraquat (PQ)-induced Lung Injury in Mice By Altering Inflammation, Oxidative Stress and Fibrosis Through NF-κB Pathway. Biochem Biophys Res Commun. 2018 09 3;503(1):94-101. PubMed PMID: 29852175.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angptl2 deficiency attenuates paraquat (PQ)-induced lung injury in mice by altering inflammation, oxidative stress and fibrosis through NF-κB pathway. AU - Yang,Wei, AU - Liu,Wen, AU - Yu,Wei, AU - Fei,Dongsheng, AU - Meng,Xianglin, AU - Yang,Songlin, AU - Meng,Shishuai, AU - Zhao,Mingyan, Y1 - 2018/06/11/ PY - 2018/05/11/received PY - 2018/05/28/accepted PY - 2018/6/1/pubmed PY - 2018/11/27/medline PY - 2018/6/1/entrez KW - Angptl2 KW - Fibrosis KW - Inflammation KW - Oxidative stress KW - Paraquat (PQ) SP - 94 EP - 101 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 503 IS - 1 N2 - Paraquat (PQ) is one of the most extensively used herbicides, possessing high toxicity for humans and animals. The lung is the main target organ by the poisoning of PQ resulting in acute lung injury. Nonetheless, molecular mechanisms underlying PQ-induced lung injury remain unclear. Here, we ask if angiopoietin-like protein 2 (Angptl2), a pro-inflammatory protein, contributes to inflammation that accelerates acute lung injury. The results indicated that abundant Angptl2 expression was observed in lung tissues of PQ-treated mice. Histological analysis revealed that PQ-induced histological changes were alleviated by Angptl2 knockout (Angptl2-/-). Angptl2-/- in PQ-treated mice attenuated acute lung injury progression by reducing the number of total cells, total leukocytes, neutrophils and macrophages in bronchoalveolar lavage fluid (BALF) and reducing inflammatory response through the inactivation of nuclear factor kappa B (NF-κB) pathway. Angptl2-/- reduced oxidative stress in PQ-treated mice, as evidenced by the enhanced superoxide dismutase (SOD) activity and reduced malondialdehyde (MDA) levels in serum or lung tissue samples, which was accompanied with increased expressions of nuclear respiratory factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1). PQ-induced fibrosis was also improved in Angptl2-/- mice by decreasing pulmonary transforming growth factor (TGF)-β1 expressions. In vitro, we found that Angptl2 knockdown-suppressed inflammation, oxidative stress and fibrosis was restored by increasing NF-κB activation in PQ-incubated A549 cells; however, the results above were significantly reversed by inactivating NF-κB using its inhibitor, Bay 11-7085 or LY2409881. Therefore, Angptl2 could provide therapeutic effects on PQ-induced acute lung injury through inhibiting inflammation, oxidative stress and fibrosis by regulating NF-κB pathway. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/29852175/Angptl2_deficiency_attenuates_paraquat__PQ__induced_lung_injury_in_mice_by_altering_inflammation_oxidative_stress_and_fibrosis_through_NF_κB_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(18)31262-2 DB - PRIME DP - Unbound Medicine ER -