WSB1, a Hypoxia-Inducible E3 Ligase, Promotes Myofibroblast Accumulation and Attenuates Alveolar Epithelial Regeneration in Mouse Lung Fibrosis

In this study, we explored the expression, cellular distribution and function of WSB1 in bleomycin (BLM)-induced mouse lung injury and fibrosis. WSB1 expression was highly induced by BLM injury and correlated with the progression of lung fibrosis. Significantly, conditional deletion of Wsb1 in adult mice ameliorated BLM-induced pulmonary fibrosis. Phenotypically, Wsb1-deficient mice exhibited reduced lipofibroblast (LIF) to MYF transition, but enhanced alveolar type 2 (AT2) proliferation and differentiation into AT1 following BLM injury. Proteomic analysis of mouse lung tissues identified Caveolin 2 as a potential downstream target of WSB1, contributing to BLM-induced epithelial injury repair and fibrosis. Our findings unravel a vital role for WSB1 induction in lung injury repair, thus highlighting it as a potential therapeutic target for pulmonary fibrosis.PMID:38325552 | DOI:10.1016/j.ajpath.2024.01.010

Source: Am J Pathol - February 7, 2024 Category: Pathology Authors: Lei Chong Lihui Zou Liyan Xiang Xinyue Song Wanqi Miao Xihua Yan Ming Xu Gongxia Ling Elie El Agha Saverio Bellusci Zhenkun Lou Hailin Zhang Jin-San Zhang Source Type: research