Figure 7.
Summary of in vitro and ex vivo systems to mimic alveolar epithelial and fibroblast damage and dysfunction in the IPF lung. While IPF fibroblasts and bleomycin treated NHLFs exhibit some hallmarks of senescence, these cells do not appear to demonstrate a phenotype of Cdkn2a/p16ink4a expression, ECM deposition, or secretion of fibrotic mediators such as TIMP1. Rather, the SASP of senescent, aberrant epithelial cells drives a fibrotic phenotype in NHLFs that is consistent with progressive fibrosis. Development of senolytic agents presents an opportunity for therapeutic impact early in disease pathogenesis and with an orthogonal mechanism than the fibroblast targeting standard of care, Nintedanib. Image created with https://www.biorender.com/.