HIP/PAP protects against bleomycin-induced lung injury and inflammation and subsequent fibrosis in mice

被引:8
|
作者
Zheng, Xiaoyan [1 ]
Li, Qian [1 ]
Tian, Hong [2 ]
Li, Hanchao [1 ]
Lv, Yifei [3 ]
Wang, Yanhua [1 ]
He, Lan [1 ]
Huo, Yongwei [2 ]
Hao, Zhiming [1 ]
机构
[1] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Rheumatol, 277 Yantaxilu, Xian, Shaanxi, Peoples R China
[2] Xi An Jiao Tong Univ, Sch Med, Res Ctr Reprod Med, 76 Yantaxilu, Xian, Shaanxi, Peoples R China
[3] Xi An Jiao Tong Univ, Affiliated Hosp 3, Dept Gastroenterol, Xian, Peoples R China
基金
中国国家自然科学基金;
关键词
fibrosis; HIP; PAP; inflammation; lung; mouse; IDIOPATHIC PULMONARY-FIBROSIS; TNF-ALPHA; MESENCHYMAL TRANSITION; MICROVASCULAR INJURY; OXIDATIVE STRESS; GROWTH-FACTOR; IN-VITRO; ACTIVATION; EXPRESSION; PANCREATITIS;
D O I
10.1111/jcmm.15334
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), a C-type lectin, exerts anti-oxidative, anti-inflammatory, bactericidal, anti-apoptotic, and mitogenic functions in several cell types and tissues. In this study, we explored the role of HIP/PAP in pulmonary fibrosis (PF). Expression of HIP/PAP and its murine counterpart, Reg3B, was markedly increased in fibrotic human and mouse lung tissues. Adenovirus-mediated HIP/PAP expression markedly alleviated bleomycin (BLM)-induced lung injury, inflammation, and fibrosis in mice. Adenovirus-mediated HIP/PAP expression alleviated oxidative injury and lessened the decrease in pulmonary superoxide dismutase (SOD) activity in BLM-treated mice, increased pulmonary SOD expression in normal mice, and HIP/PAP upregulated SOD expression in cultured human alveolar epithelial cells (A549) and human lung fibroblasts (HLF-1). Moreover, in vitro experiments showed that HIP/PAP suppressed the growth of HLF-1 and ameliorated the H2O2-induced apoptosis of human alveolar epithelial cells (A549 and HPAEpiC) and human pulmonary microvascular endothelial cells (HPMVEC). In HLF-1, A549, HPAEpiC, and HPMVEC cells, HIP/PAP did not affect the basal levels, but alleviated the TGF-beta 1-induced down-regulation of the epithelial/endothelial markers E-cadherin and vE-cadherin and the over-expression of mesenchymal markers, such as alpha-SMA and vimentin. In conclusion, HIP/PAP was found to serve as a potent protective factor in lung injury, inflammation, and fibrosis by attenuating oxidative injury, promoting the regeneration of alveolar epithelial cells, and antagonizing the pro-fibrotic actions of the TGF-beta 1/Smad signaling pathway.
引用
收藏
页码:6804 / 6821
页数:18
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