Ubiquitin-proteasome system in the molecular mechanisms of lung injury and pulmonary fibrosis

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Ubiquitin-proteasome system in lung injury and fibrosisUbiquitin and multiubiquitin were upregulated in lung tissues from patients with idiopathic pulmonary fibrosis (IPF). There were apoptotic epithelial cells in lung tissues from IPF. Multiubiquitin was detected in lung epithelial cells of bleomycin-induced pulmonary fibrosis in mice. Proteasome inhibitor induced apoptosis in lung epithelia cells in vitro, in which multiubiquitin was detected in apoptotic cells. Multiubiquitin was also detected by western blot analysis. These results suggest that epithelial cell apoptosis is involved in lung injury and pulmonary fibrosis in mouse and human, and that malfunction of ubiquitin-proteasome system may be involved in this apoptosis.The interaction of p53, MDM2, and SUMO1 in lung injury and fibrosisThe expression of p53, MDM2, and SUMO1 were upregulated in lung epithelial cells from patients with IPF and from bleomycin-induced pulmonary fibrosis in mice. The upregulation of these proteins were also detected by western blot analysis. MDM2 is E3 ligase for p53 and degenerate through ubiqutination. SUMO1 regulates self-ubiquitination of MDM2. We found that p53, MDM2 and SUMO1 interact each other and degrade through ubiquitin-proteasome system in lung epithelia cells. Ubiquitin-proteasome system is involved in p53-induced apoptosis of lung epithelial cells.