博莱霉素
炎症
肺纤维化
上皮-间质转换
促炎细胞因子
氧化应激
肺
纤维化
化学
医学
药理学
特发性肺纤维化
癌症研究
免疫学
病理
内科学
癌症
转移
化疗
作者
Wenhui Ma,Meng Li,Haifeng Ma,Wei Li,Li Liu,Yan Yin,Xiaoming Zhou,Gang Hou
出处
期刊:Life Sciences
[Elsevier]
日期:2020-01-01
卷期号:241: 117139-117139
被引量:43
标识
DOI:10.1016/j.lfs.2019.117139
摘要
Idiopathic pulmonary fibrosis (IPF) is a serious lung problem with advancing and diffusive pulmonary fibrosis as the pathologic basis, and with oxidative stress and inflammation as the key pathogenesis. Glycyl-L-histidyl-l-lysine (GHK) is a tripeptide participating into wound healing and regeneration. GHK-Cu complexes improve GHK bioavailability. Thus, the current study aimed to explore the therapeutic role of GHK-Cu on bleomycin (BLM)-induced pulmonary fibrosis in a mouse model. BLM (3 mg/kg) was administered via tracheal instillation (TI) to induce a pulmonary fibrosis model in C57BL/6j mice 21 days after the challenge of BLM. GHK-Cu was injected intraperitoneally (i.p.) at different dosage of 0.2, 2 and 20 μg/g/day in 0.5 ml PBS on alternate day. The histological changes, inflammation response, the collagen deposition and epithelial-mesenchymal transition (EMT) was evaluated in the lung tissue. EMT was evaluated by ɑ-SMA and fibronectin expression in the lung tissue. NF-κB p65, Nrf2 and TGFβ1/Smad2/3 signalling pathways were detected by immunoblotting analysis. GHK-Cu complex inhibited BLM-induced inflammatory and fibrotic pathological changes, alleviated the inflammatory response in the BALF by reducing the levels of the inflammatory cytokines, TNF-ɑ and IL-6 and the activity of MPO as well as reduced collagen deposition. In addition, the GHK-Cu treatment significantly reversed the MMP-9/TIMP-1 imbalance and partially prevented EMT via Nrf2, NF-κB and TGFβ1 pathways, as well as Smad2/3 phosphorylation. GHK-Cu presented a protective effect in BLM-induced inflammation and oxidative stress by inhibiting EMT progression and suppressing TGFβ1/Smad2/3 signalling in pulmonary fibrosis.
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