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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\u2010mediated HIP\/PAP expression markedly alleviated bleomycin (BLM)\u2010induced lung injury, inflammation, and fibrosis in mice. Adenovirus\u2010mediated HIP\/PAP expression alleviated oxidative injury and lessened the decrease in pulmonary superoxide dismutase (SOD) activity in BLM\u2010treated 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\u20101). Moreover, in vitro experiments showed that HIP\/PAP suppressed the growth of HLF\u20101 and ameliorated the H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced apoptosis of human alveolar epithelial cells (A549 and HPAEpiC) and human pulmonary microvascular endothelial cells (HPMVEC). In HLF\u20101, A549, HPAEpiC, and HPMVEC cells, HIP\/PAP did not affect the basal levels, but alleviated the TGF\u2010\u03b21\u2010induced down\u2010regulation of the epithelial\/endothelial markers E\u2010cadherin and vE\u2010cadherin and the over\u2010expression of mesenchymal markers, such as \u03b1\u2010SMA 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\u2010fibrotic actions of the TGF\u2010\u03b21\/Smad signaling pathway.<\/jats:p>","DOI":"10.1111\/jcmm.15334","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T18:43:18Z","timestamp":1588272198000},"page":"6804-6821","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["HIP\/PAP protects against bleomycin\u2010induced lung injury and inflammation and subsequent fibrosis in mice"],"prefix":"10.1111","volume":"24","author":[{"given":"Xiaoyan","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Rheumatology The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 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