How p21 promotes pulmonary fibrosis?
p21-positive senescent cells are enriched in pulmonary fibrosis, but the exact contribution of p21 to fibrosis remains unclear.
The researchers uncover using mouse genetic that an aggravating role of p21 in tissue fibrosis, promoting extracellular matrix (ECM) expression, senescent cell frequency and immune invasion.
Depletion of global or inducible p21 after disease onset limits bleomycin-induced pulmonary fibrosis in mice. p21 depletion also reduces senescent cell frequency and inflammatory responses in fibrotic lungs.
The authors demonstrate that p21 regulates ECM expression in both senescent and proliferating cells in a CDK4- and Rb phosphorylation-dependent manner.
https://www.embopress.org/doi/full/10.1038/s44318-024-00246-7
