HECTD1-mediated SFTPB overexpression in fibrotic lung induced by silica.

Alveolar epithelial cells type 2 are lung progenitor and secretory cells capable of secreting four surfactant proteins, namely surfactant protein A (SFTPA), surfactant protein B (SFTPB), surfactant protein C (SFTPC), and surfactant protein D (SFTPD). Among these proteins, SFTPB not only participates in the composition of surfactant proteins but also has important immune functions. In occupational dust exposure, dust entering the bronchi and alveoli can come into direct contact and stimulate AT2. To investigate the expression of SFTPB in fibrotic lungs, we constructed a mouse pulmonary fibrosis model using silica and detected the spatial expression of SFTPB protein and SFTPB mRNA in lung sections. Herein, we observed an increase in SFTPB production from AT2 in SiO2-exposed mice without a corresponding increase in mRNA levels in the lung sections. Pulmonary fibrosis continued to progress in mice on day 112 after modeling. During the progression of pulmonary fibrosis, the protein level of SFTPB was always higher than that of the control mice, accompanied by increased HECT domain E3 ubiquitin protein ligase 1 (HECTD1) and ubiquitin (Ub). HECTD1 knockdown can partially reverse the increase in SFTPB in AT2 induced by silica. Therefore, we concluded that HECTD1 mediated SFTPB overexpression in silica-induced fibrotic lungs.