Progressive pulmonary fibrosis in a murine model of Hermansky-Pudlak syndrome

• DOI: 10.1186/s12931-022-02002-z
• Publication Date: 2022-05-04T11:02:58Z
• Authors: Shachar Abudi-Sin...; Steven P. Bodine; Tadafumi Yokoyama; Nathanial J. Tolman; Michal Tyrlik; Lauren C. Testa; Chen G. Han; Heidi M. Dorward; Stephen M. Wincov...; Yair Anikster; William A. Gahl; Resat Cinar; Bernadette R. Goc...; May Christine V. ...
• Keywords: Hermansky–Pudlak syndrome

Abstract Background HPS-1 is a genetic type of Hermansky-Pudlak syndrome (HPS) with highly penetrant pulmonary fibrosis (HPSPF), restrictive lung disease that similar to idiopathic (IPF). Hps1 ep/ep (pale ear) naturally occurring mouse model exhibits high sensitivity bleomycin-induced (PF). Traditional methods administering bleomycin as an intratracheal (IT) route induce PF in this often lead severe acute injury and mortality rates, complicating studies focusing on pathobiological mechanisms or exploration therapeutic options for HPSPF. Methods To develop murine HPSPF closely mimics the progression human fibrosis, we investigated effects systemic delivery mice using subcutaneous minipump compared results oropharyngeal bleomycin. Results Our study revealed induced limited, inflammation resolved. The distinct inflammatory phase preceded slow, gradually progressive fibrogenesis was shown be both time-dependent dose-dependent. exhibited characteristics better resembles focal regions were predominantly found peribronchovascular areas subpleural regions; central contained relatively less fibrosis. Conclusion This provides preclinical tool will allow researchers mechanism HPS provide platform development therapeutics treat method can applied IPF other monogenic disorders