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

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 H2 O2 -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-β1-induced down-regulation of the epithelial/endothelial markers E-cadherin and vE-cadherin and the over-expression of mesenchymal markers, such as α-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-β1/Smad signaling pathway.

Zheng X ，Li Q ，Tian H ，Li H ，Lv Y ，Wang Y ，He L ，Huo Y ，Hao Z ... -  《-》

Hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) confers protection against hepatic fibrosis through downregulation of transforming growth factor β receptor II.

Li Q ，Li H ，Lv Y ，Zhang Q ，Zhang X ，Li S ，Zheng X ，Wang Y ，Hao Z ... -  《-》

Paeoniflorin suppresses TGF-β mediated epithelial-mesenchymal transition in pulmonary fibrosis through a Smad-dependent pathway.

Ji Y ，Dou YN ，Zhao QW ，Zhang JZ ，Yang Y ，Wang T ，Xia YF ，Dai Y ，Wei ZF ... -  《-》

Hydrogen inhalation attenuated bleomycin-induced pulmonary fibrosis by inhibiting transforming growth factor-β1 and relevant oxidative stress and epithelial-to-mesenchymal transition.

• What is the central question of this study? The aim was to explore the effects and underlying mechanisms of H2 on bleomycin-induced pulmonary fibrosis. • What are the main findings and its importance? Our results indicate that, in bleomycin-induced pulmonary fibrosis, H2 inhalation attenuated oxidative stress and reversed the pulmonary epithelial-to-mesenchymal transition process by reducing reactive oxygen species production and inhibiting the expression of transforming growth factor-β1, α-smooth muscle actin and collagen I to improve fibrotic injury and exert anti-fibrogenic effects. Thus, H2 inhalation has promising therapeutic potential as a useful adjuvant treatment for patients with idiopathic pulmonary fibrosis, which deserves further study and evaluation. Hydrogen (H2 ) can protect against tissue damage. The effect of H2 inhalation therapy on the pathogenesis of pulmonary fibrosis remains unknown. This study was designed to explore the effects and underlying mechanisms of H2 inhalation on bleomycin (BLM)-induced pulmonary fibrosis. A rat model of pulmonary fibrosis was established with BLM. Rats were randomly divided into control and H2 inhalation groups. Haematoxylin and Eosin staining and Mason's Trichrome staining were performed to evaluate pulmonary fibrosis injury, inflammatory cell infiltration, structural disorder and collagen deposition. qRT-PCR and western blot assays were used to determine the expression of TNF-α, TGF-β1, α-SMA, E-cadherin, N-cadherin, vimentin, VEGF and collagen type I at both mRNA and protein levels. The contents of reactive oxygen species, TGF-β1, TNF-α, malondialdehyde and hydroxyproline were determined with biochemical test kits or ELISA kits. Bleomycin-stimulated rats exhibited typical symptoms of pulmonary fibrosis, which featured an increase in collagen deposition, alveolitis, fibrosis and parenchymal structural disorder in the lung. However, BLM-induced oxidative stress was attenuated by H2 inhalation therapy, which reduced the contents of reactive oxygen species, malondialdehyde and hydroxyproline, enhanced the activity of glutathione peroxidase and decreased the expression of TGF-β1 and TNF-α. In addition, H2 inhalation also inhibited BLM-induced epithelial-to-mesenchymal transition by inhibiting TGF-β1, increasing the expression level of the epithelial cell marker E-cadherin, and decreasing the expression level of the mesenchymal cell marker vimentin in a time-dependent manner. In addition, H2 inhalation downregulated α-SMA expression and suppressed collagen I generation, exerting anti-fibrogenic effects. Hydrogen inhalation therapy attenuates BLM-induced pulmonary fibrosis by inhibiting TGF-β1, relevant oxidative stress and epithelial-to-mesenchymal transition.

Gao L ，Jiang D ，Geng J ，Dong R ，Dai H ... -  《-》

Dasatinib Suppresses TGFβ-Mediated Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells and Inhibits Pulmonary Fibrosis.

Kanemaru R ，Takahashi F ，Kato M ，Mitsuishi Y ，Tajima K ，Ihara H ，Hidayat M ，Wirawan A ，Koinuma Y ，Hayakawa D ，Yagishita S ，Ko R ，Sato T ，Harada N ，Kodama Y ，Nurwidya F ，Sasaki S ，Niwa SI ，Takahashi K ... -  《-》