Atg5 inhibits fibroblast activation and promotes alveolar regeneration to alleviate pulmonary fibrosis

Under injury, autophagy often initiated to maintain cell survival and promote tissue regeneration. Here, we show that autophagy, a conserved cellular process, is upregulated in the mesenchymal cells of lung tissue in IPF patients and in a murine model of bleomycin-induced fibrosis.

Our findings indicate that Atg5, a crucial autophagy-related gene, when conditionally deleted in mesenchymal cells, renders mice more susceptible to bleomycin-induced fibrosis. Mechanistically, this is mainly due to the loss of Atg5 exacerbating the activation of fibroblasts induced by TGF-β1, the proliferation of myofibroblasts, and the deposition of extracellular matrix. Intriguingly, as an important niche for alveolar type 2 (AT2) cells, the absence of Atg5 impairing the secretion of factors essential for AT2 cell proliferation and differentiation.