| First Author | Miura Y | Year | 2022 |
| Journal | Life Sci Alliance | Volume | 5 |
| Issue | 1 | PubMed ID | 34728556 |
| Mgi Jnum | J:322119 | Mgi Id | MGI:6826641 |
| Doi | 10.26508/lsa.202101059 | Citation | Miura Y, et al. (2022) Bimodal fibrosis in a novel mouse model of bleomycin-induced usual interstitial pneumonia. Life Sci Alliance 5(1) |
| abstractText | Idiopathic pulmonary fibrosis is pathologically represented by usual interstitial pneumonia (UIP). Conventional bleomycin models used to study pathogenic mechanisms of pulmonary fibrosis display transient inflammation and fibrosis, so their relevance to UIP is limited. We developed a novel chronic induced-UIP (iUIP) model, inducing fibrosis in D1CCxD1BC transgenic mice by intra-tracheal instillation of bleomycin mixed with microbubbles followed by sonoporation (BMS). A bimodal fibrotic lung disease was observed over 14 wk, with an acute phase similar to nonspecific interstitial pneumonia (NSIP), followed by partial remission and a chronic fibrotic phase with honeycombing similar to UIP. In this secondary phase, we observed poor vascularization despite elevated PDGFRbeta expression. gamma2PF- and MMP7-positive epithelial cells, consistent with an invasive phenotype, were predominantly adjacent to fibrotic areas. Most invasive cells were Scgb1a1 and/or Krt5 positive. This iUIP mouse model displays key features of idiopathic pulmonary fibrosis and has identified potential mechanisms contributing to the onset of NSIP and progression to UIP. The model will provide a useful tool for the assessment of therapeutic interventions to oppose acute and chronic fibrosis. |
