Angptl2 deficiency attenuates paraquat (PQ)-induced lung injury in mice by altering inflammation, oxidative stress and fibrosis through NF-κB pathway.

作者：Wei Yang, Wen Liu, Wei Yu, Dong-sheng Fei, Xianglin Meng, Songlin Yang, Shishuai Meng, Mingyan Zhao · 发表于：Biochemical and Biophysical Research Communications - BBRC · 年份：2018 · DOI：10.1016/j.bbrc.2018.05.186 · 被引用次数：29 · 研究领域：Chemistry、Medicine

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 inflammatio...